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8th Conference on Retroviruses and Opportunistic InfectionsChicago, IL - February 4 -February 8, 2001 |
Cite as: Conf Retroviruses Opportunistic Infect. 2001 Feb 4-8;8th:Abstract No. xx
| Session 1 — Opening Session |
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| L1 | BERNARD FIELDS MEMORIAL LECTURE: AVOIDANCE OF ANTIBODY RECOGNITION BY SIV- AND HIV-ENCODED ENVELOPE PROTEINS Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:279 (abstract no. L1) Desrosiers R Our results indicate that a variety of mutational changes can impart neutralization sensitivity and that these changes result in more effective immunological control. These results are important at a fundamental level for better understanding of how immune evasion strategies contribute to pathogenesis. |
| L2 | KEYNOTE LECTURE: HETEROGENEITY AND PUBLIC HEALTH IN THE GLOBAL HIV/AIDS EPIDEMIC Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:279 (abstract no. L2) DeCock K The global response to HIV/AIDS has to accommodate recent biomedical developments such as interventions to prevent mother-to-child transmission, HIV testing technologies, and antiretroviral therapy, as well as epidemiologic trends such as behavioral changes in men who have sex with men and the disproportionate impact of HIV/AIDS in sub-Saharan Africa. If we are to influence the course of the international epidemic and exploit recent technical advances, greater investment will be required in public health and public health infrastructure whose importance have been underemphasized in the necessary multisectoral approach. |
| L3 | KEYNOTE LECTURE: FROM TALK TO ACTION IN FIGHTING AIDS IN DEVELOPING COUNTRIES Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:279 (abstract no. L3) Sachs JD The total level of donor support necessary to introduce such a comprehensive effort may be estimated at around $7.5 - $10 billion per year. This would permit millions of people in the very poorest countries to receive HAART, and would also finance the scaling up of other needed interventions. It would be readily affordable by the high-income countries, as it would constitute less than 0.05% of gross national product of these countries (now close to $24 trillion annually). |
| Session 2 — State-of-the-Art Lecture Closing the Door on HIV Entry |
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| L4 | CLOSING THE DOOR ON HIV ENTRY Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:280 (abstract no. L4) Doms R Details of the entry process suggest that the use of coreceptor antagonists may slow the rate of membrane fusion by reducing receptor density, thereby prolonging exposure of conserved, critically important domains such as those on the surface of the triple stranded coiled-coil in the gp41 subunit of Env. Combination chemotherapy with different classes of entry inhibitors may therefore result in synergistic inhibition of virus infection. |
| Session 3 — State-of-the-Art Lecture Viral Reservoirs and Ongoing Virus Replication in Patients on HAART: Implications for Clinical Management |
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| L5 | VIRAL RESERVOIRS AND ONGOING VIRUS REPLICATION IN PATIENTS ON HAART: IMPLICATIONS FOR CLINICAL MANAGEMENT Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:280 (abstract no. L5) Siliciano R Low-level viremia in patients on HAART with <50 copies/ml of HIV-1 RNA results primarily from release of archival, pre-HAART viruses rather than new, HAART-selected, partially resistant mutants. The results indicate that long-term suppression on HAART may be possible. However, the continued release of archival, drug-resistant viruses selected by prior non-suppressive regimens may limit the effectiveness of the "recycling" of antiretroviral drugs. |
| Session 4 — Slide NeuroAIDS |
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| 1 | Viral persistence in the CSF under HAART despite adequate plasma response associated with symptomatic HIV-1 infection of the CNS. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8;8:43 (abstract no. 1) Eggers C, Hertogs K, Sturenburg HJ, Stellbrink HJ, Van Lunzen J; Univ Hosp Hamburg, Germany Antiviral treatment must consider the CNS to prevent or treat HIV dementia and to respond to the role of the CNS as a viral reservoir. In most patients HAART leads to a rapid decay of plasma as well as CSF virus. It was suggested that the source of the CSF virus in these patients is outside the CSF spaces. |
| 2 | Cerebrospinal fluid T lymphocytes: expression of phenotypic activation markers in HIV infection. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:43 (abstract no. 2) Price RW, Neuenburg J, Nilsson A, Pearce R, Grant RM, Hebert S, McCune JM, Sinclair E; Univ of California, San Francisco. The cerebrospinal fluid (CSF) space can be a site of compartmentalized HIV infection with respect to both virus and lymphocyte traffic. This study was undertaken to assess expression of activation markers on T cells in CSF compared to blood in HIV infection, and to compare this expression to that in HIV-... |
| 3 | Cerebrospinal fluid HIV-1 RNA levels peak during primary HIV-1 infection. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:43 (abstract no. 3) Pilcher CD, Robertson K, Hall C, Menezes P, Fiscus SA, Hicks CB, Eron JJ; Univ of North Carolina, Chapel Hill. Primary HIV infection (PHI) is characterized by rapid infection of lymphoid organs and secondary dissemination to peripheral tissues. In this study we investigated the timing and extent of viral dissemination to the CNS during PHI and assessed the effects of ART initiated during PHI within the CNS. |
| 4 | Macrophage chemotaxis and activation by fractalkine: a role for neuronal injury in brain immunity during HIV-1 associated dementia. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:44 (abstract no. 4) Zheng J, Lopez A, Erichsen D, Bauer M, Cotter RL, Ryan LA, Williams C, Ghorpade A, Morgello S, Gendelman HE; Univ of Nebraska Med Ctr, Omaha. Mononuclear phagocyte (MP; brain macrophage and microglia) activation and neuronal injury are major features of HIV-1 encephalitis (HIVE), the histopathological correlate for HIV-1-associated dementia (HAD). MP activation plays a significant role in disease causation and propagation. |
| 5 | Tropism of primary brain-derived HIV-1 isolates for microglia and macrophages and relationship to neuropathicity. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:44 (abstract no. 5) Gorry P, Ohagen A, Holm G, Birch C, Bell J, Kunstman K, Wolinsky S, Gabuzda D; Dana-Farber Cancer Inst, Boston, MA. The viral determinants that underlie neurotropism and neurovirulence of HIV-1 are unknown, due in part to limited studies on primary brain isolates. To better understand neuropathogenic mechanisms of HIV-1, we isolated primary viruses from brain, CSF, spinal cord, spleen, and lymph node autopsy samples ... |
| 6 | Differential regulation of CCR5 and cxcr 4 on macrophages and microglia: implications for HIV-1 pathogenesis in the CNS and other tissue reservoirs. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:44 (abstract no. 6) Wang J, Crawford K, Gabuzda D; Dana-Farber Cancer Inst. Macrophages, microglia, and other mononuclear phagocytes are targets for HIV-1 infection and serve as vehicles for virus dissemination and persistence. Methods: To understand host factors that influence HIV-1 pathogenesis in the CNS and other tissue reservoirs by regulating expression and function of HIV-1 ... |
| 7 | Elevated levels of soluble CD14 and TNF-α receptor two in HIV-1 infected patients with brain atrophy. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:44 (abstract no. 7) Ryan LA, Zheng J, Brester M, Bohac D, Hahn F, Gendelman HE, Swindells S; Univ of Nebraska Med Ctr, Omaha. The role of peripheral immune responses in the pathogenesis of HIV-1 associated dementia (HAD) was investigated through a prospective study of 28 patients with advanced HIV-1 disease with or without neurological dysfunction. All patients were on potent antiretroviral therapy. Methods: Clinical, immune, ... |
| 8 | Shift of prevalence and selected characteristic in HIV-1-related neurologic disorders in HAART era: data from Italian Register Investigative Neuro Aids (IRINA). Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:45 (abstract no. 8) Antinori A, Ammassari A, Cinque P, Toma L, Govoni A, Soldani F, Giancola ML, Grisetti S, Pierotti C, Fausti C, Finazzi MG, Bini T, Del Grosso B, Cristiano L, Corsi P, Fasulo G, Mena M, Guaraldi G, Arcidiacono MI, Monno L, Gigli B, Fibbia GC, Gentile M, Mastroianni A, Speranza F, d'Arminio Monforte A, Rezza G, Ippolito G; Italian Register Investigative Neuro AIDS, Natl Inst of Infectious Diseases L Spallanzani, Rome, Italy. This study involved evaluation of the prevalence, clinical characteristics, and relationship with antiretroviral therapy in newly registered HIV-1-related neurologic diseases in Italy . Methods: Multicenter study conducted in 65 clinical centers from January 2000. Main characteristics at neurological ... |
| 9 | Lactate concentrations distinguish between nucleoside neuropathy and HIV distal symmetrical sensory polyneuropathy. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:45 (abstract no. 9) Brew B, Tisch S, Law M; St Vincent's Hosp. The clinical distinction between nucleoside neuropathy (NN), which may be related to mitochondrial dysfunction, and distal symmetrical polyneuropathy (DSPN), which may be related to active viral replication, is difficult. We sought to determine whether an elevated serum lactate concentration (a marker of ... |
| 10 | Clinical course and prognostic factors of AIDS-associated progressive multifocal leukoencephalopathy (PML) in patients treated with HAART (GESIDA 11/99). Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:45 (abstract no. 10) Berenguer J, Miralles P, Arrizabalaga J, Ribera E, Dronda F, Baraia J, Domingo P, Marquez M, Rodriguez-Arrondo FJ, Laguna F, Rubio R, Lopez-Aldeguer J, De Miguel V; Hosp G Maranon, Madrid. We analyzed survival, neurologic function and prognostic factors of patients with AIDS-associated PML treated with HAART. Methods: 118 patients with PML treated with HAART from 11 centers in Spain were included in the study. The diagnosis of PML was established by brain biopsy and/or PCR confirmation in 42 ... |
| Session 5 — Slide Antiretroviral Chemotherapy |
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| 11 | DPC 681 and DPC 684: resistance and cross-resistance profiles of second generation HIV protease inhibitors. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:46 (abstract no. 11) Erickson-Viitanen S, Kaltenbach R, Getman D, Garber S, Logue K, Jeffrey S, Bacheler L, Diamond S, Albright A, Gonzalez-Scarano F, Davies M, Harris G, Trainor G; DuPont Pharmaceuticals Co, Wilmington, DE. HIV protease inhibitors (PIs) are important components of many HAART regimens. However, development of phenotypic and/or genotypic resistance can occur, including cross- resistance to other PIs. Development of resistance takes place because trough levels of free drug are inadequate. |
| 12 | A femtomolar HIV-1 protease inhibitor with subnanomolar activity against multidrug resistant HIV- 1 strains. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:46 (abstract no. 12) Erickson J, Gulnik S, Suvorov L, Gustchina E, Xie D, Wang G, Eissenstat MA, De Bethune MP, Jonckheere H, De Meyer S, Azijn H, Pauwels R, Wigerinck P, Surleraux D, Verschueren W, Tahri A, Ghosh A, Yoshimura K, Mitsuya H; Tibotec, Rockville, MD. The widespread clinical use of HIV-1 reverse transcriptase and protease inhibitors (PIs) has resulted in the emergence of resistant strains of HIV-1 that severely compromise the usefulness of such drugs. Cross-resistance within a mechanistic class of inhibitors is the rule, rather than the exception, and ... |
| 13 | TMC120, a new non-nucleoside reverse transcriptase inhibitor, is a potent antiretroviral in treatment naïve, HIV-1 infected subjects. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:46 (abstract no. 13) Gruzdev B, Horban A, Boron-Kaczmarska A, Gille D, Van't Klooster G, Pauwels R; Infectious Disease Hosp, Moscow, Russia. TMC120 (R147681), a dianilinopyrimidine (DAPY) derivative, is a novel, non- nucleoside reverse transcriptase inhibitor (NNRTI) with equipotent in vitro activity (IC50 = 1-10 nM) against wild-type HIV-1 and NNRTI-resistant variants encoding K103N, Y181C or G190A/S mutations. Methods: Randomized, double-blind... |
| 14 | A 14-day assessment of the safety, pharmacokinetics, and antiviral activity of T-1249, a peptide inhibitor of membrane fusion. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:47 (abstract no. 14) Eron J, Merigan T, Kilby M, Yangco B, Gleavy J, Rusnak P, Dimassimo B, Smith R, Baker B, Duff F, Drucker J, Matthews T, Hopkins S; Univ of North Carolina at Chapel Hill. T-1249 is a peptide fusion inhibitor developed as a follow on compound to T-20. In laboratory and animal studies, T-1249 has demonstrated unique potency against a broad range of HIV-1, HIV-2, and SIV isolates, favorable PK characteristics, and a non-overlapping resistance profile with respect to T-20. |
| 15 | AI424-007: 48-week safety and efficacy results from a phase II study of a once-daily HIV-1 protease inhibitor (PI), BMS-232632. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:47 (abstract no. 15) Squires K, Gatell J, Piliero P, Sanne I, Wood R, Schnittman SM; Univ of Alabama at Birmingham. BMS-232632 (BMS) is a PI with potent activity in vitro (EC50 2-5 nM), a favorable resistance profile, and a PK profile that supports once-daily dosing. Methods: This phase II, 2-staged randomized study compares the safety and antiretroviral activity of 3 dose levels of BMS with nelfinavir (NFV) 750 mg tid ... |
| 16 | Antiretroviral therapy (ART) plus cyclophosphamide (CTX) to diminish HIV DNA in lymphoid tissue. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:47 (abstract no. 16) Bartlett JA, Silberman M, Miralles GD, Sevin A, Pruitt S, Ottinger J, Gryszowka V, Fiscus S, Bucy RP; Duke Univ Med Ctr, Durham, NC. ART can decrease HIV RNA in peripheral blood and lymphoid tissue but HIV DNA does not decrease in either compartment. Methods: ART ( stavudine , lamivudine and nelfinavir) was initiated in 10 treatment-naïve subjects with CD4 cells >200/mm3. Subjects received ART until plasma HIV RNA ... |
| 17 | Prospective, randomized, controlled phase II study of highly active antiretroviral therapy (HAART) with continuous IV (CIV) or subcutaneous (SC) interleukin-2 (IL-2) in HIV-infected patients with CD4+ counts of 50-350 cells/mm3: ACTG 328-final results at 84 weeks. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:48 (abstract no. 17) Mitsuyasu R, Pollard R, Gelman R, Weng D; Univ of California, Los Angeles. The objectives of this study were to ascertain the effects of IL-2 given by either CIV or SC routes added to HAART vs HAART alone on CD4 response, immune phenotype and function, antiviral effectiveness of HAART, tolerability and quality of life in patients (pts) with advanced HIV. Methods: 204 protease ... |
| 18 | Two randomized, controlled, equivalence trials of emtricitibine (FTC) to lamivudine (3TC). Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:48 (abstract no. 18) Van Der Horst C, Sanne I, Wakeford C, Quinn J, Rousseau F; Univ of North Carolina, Chapel Hill. FTC is a NRTI that has in vitro potency against HIV which is 4-10 times greater than 3TC and has shown approximately a 2 log10 median decrease in viral load when used at 200 mg once daily (QD) in a two week monotherapy study. To examine the efficacy and safety of FTC, we conducted two randomized, controlled ... |
| 19 | Severe liver toxicity in patients receiving two nucleoside analogues and a non-nucleoside reverse treanscriptase inhibitor. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:48 (abstract no. 19) Bartlett J; Duke Univ, Durham, NC. The use of specific antiretroviral agents may result in drug related hepatotoxicity. This toxicity has been associated with concomitant chronic viral hepatitis, alcohol use, hypersensitivity reactions and lactic acidosis. Methods: FTC-302 was a randomized, double-blind study comparing emtricitabine (FTC) ... |
| 20 | Successful substitution of protease inhibitors with efavirenz (EFV) in patients with undetectable viral loads--a prospective, randomized, multicenter, open-label study (DMP 049). Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:49 (abstract no. 20) Becker S, Rachlis A, Gill J, Dejesus E, Pierone G, Kirkland L, Koosian S, Farina D, Labriola D, Ruiz N, Bessen L, Villano S; Pacific Horizon Med Group, San Francisco, CA. Simple, potent antiretroviral (ARV) regimens that enhance adherence and are well tolerated are needed. Methods: Prospective, randomized, multicenter, open-label, 48-week study comparing the duration of viral load (VL) suppression of a continued PI + 2 NRTIs regimen to an EFV substitution regimen. |
| Session 6 — Slide Progress in AIDS Vaccine Development |
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| 21 | Safety and immunogenicity study of vCP1452/rgp160 therapeutic vaccines in patients treated with HAART for over two years. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:49 (abstract no. 21) Jin X, Ramanathan Jr M, Barsoum S, Deschenes G, Ba L, Binley J, Hurley A, El Habib R, Caudrelierl P, Zhang L, Ho DD, Markowitz M; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY. To examine whether immune responses can be adequately boosted in patients on prolonged HAART, we conducted a safety and immunogenicity study using vCP1452, a recombinant canarypox vaccine carrying HIV-1 genes (gag, pol, env and nef), together with recombinant gp160. |
| 22 | Next generation enhanced DNA and protein vaccine approaches stimulate potent immune responses against HIV antigens. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:49 (abstract no. 22) Barnett SW, Srivastava I, Stamatatos L, Zur Megede J, Otten G, Singh M, O'Hagan D, Ulmer J, Donnelly J; Chiron Corp, Emeryville, CA. The challenge for developing effective vaccines against HIV infection and disease lies in the generation of potent, broad, and durable immune responses. Toward this end, the HIV vaccine research group at Chiron has focused on increasing the potency of both DNA and adjuvanted subunit protein vaccine ... |
| 23 | Vaccination with VSV G protein exchange vectors expressing HIV env and SIV gag proteins protects rhesus macaques from challenge with highly pathogenic SHIV 89.6P. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:50 (abstract no. 23) Rose NF, Marx PA, Luckay A, Nixon DF, Moretto WJ, Donahoe SM, Rose JK; Yale Univ Sch of Med, New Haven, CT. Rhesus macaques were vaccinated and boosted with live, recombinant vesicular stomatitis virus (VSV) vectors (serotype Indiana) expressing the HIV-1 (89.6) env and SIV(mac239) gag genes. Methods: The boosts were performed with novel VSV vectors expressing the HIV and SIV proteins but expressing VSV G protein ... |
| 24 | Efficient containment of a highly pathogenic immunodeficiency virus challenge by DNA priming and recombinant MVA boosting. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:50 (abstract no. 24) Robinson H, Amara R, Moss B, McClure H, McNicholl J; Yerkes Regional Primate Res Ctr, Atlanta, GA. A vaccine consisting of DNA priming and recombinant modified vaccinia virus Ankara (rMVA) booster immunizations has contained a highly pathogenic immunodeficiency virus challenge administered by a mucosal route. Two SHIV-89.6 DNA immunizations followed by a single rMVA booster have raised high frequencies ... |
| 25 | Protection from pathogenic simian immunodeficiency virus (SIV) infection correlates with the rapid induction of SIV-specific CD8+ T cells and antibodies in rhesus macaques immunized with a live, attenuated SIV vaccine. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:50 (abstract no. 25) Metzner KJ, Moretto WJ, Donahoe SM, Paluch M, Schiller D, Lee FV, Gettie A, Marx PA, Moore JP, Ho DD, Binley J, Nixon DF, Connor RI; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY. Previously, we have shown that in vivo depletion of CD8+ T cells resulted in a 1 to 2 log increase in replication of the live, attenuated vaccine strain SIVmac239 delta nef in immunized macaques. We now show that this transient viremia results in a significant boost in both SIV-specific T cell responses ... |
| 26 | Rhesus macaques vaccinated with phage-displayed HIV-1 epitopes and subsequently infected with SHIV-89.6PD are partially protected against disease progression. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:50 (abstract no. 26) Chen X, Scala G, Liu W, Quinto I, Cohen OJ, Van Cott TC, Iwanicki M, Lewis M, Montefiori DC, Fauci AS; NIH, Bethesda, MD. Methods: To identify HIV-specific epitopes, we screened random peptide libraries (RPL) displayed on phages by using HIV-positive sera. Results: By several criteria, these peptides behaved as antigenic mimics of conformational B-cell epitopes generated in vivo in the course of the natural HIV-1 infection. |
| 27 | Delivery technologies enhance plasmid DNA vacccination in a rhesus macaque model for HIV. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:51 (abstract no. 27) Otten G, Chen M, Doe B, Kazzaz J, Lian Y, Liu H, Leung L, Ott G, Polo J, Shaefer M, Selby M, Singh M, Sun Y, Ugozzoli M, Zur Megede J, Lewis M, Miller N, Widera G, Barnett S, Donnelly J, O'Hagan D, Ulmer J; Chiron Corp, Emeryville, CA. Plasmid DNA has several features that makes it attractive as a component of an HIV vaccine. However, clinical results suggest that the modest immunogenicity of plasmid DNA may limit its protective efficacy against HIV. We have developed and tested in rhesus macaques three distinct delivery technologies ... |
| 28 | A polyvalent envelope glycoprotein vaccine elicits a broader neutralizing antibody response, but is unable to provide sterilizing protection against a heterologous SHIV infection in pigtailed macaques. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:51 (abstract no. 28) Cho MW, Kim YB, Lee MK, Gupta KC, Ross W, Plishka R, Buckler-White A, Igarashi T, Theodore T, Byrum R, Kemp C, Montefiori DC, Martin MA; NIH, Bethesda, MD. The great difficulty in eliciting broadly cross-reactive neutralizing antibodies (Nabs) against HIV-1 isolates has been attributed to several intrinsic properties of their viral envelope glycoprotein, including its complex quaternary structure, extensive glycosylation, and marked genetic variability. |
| 29 | Interactions of human dendritic cells with ALVAC-HIV (vCP205), an HIV-1 vaccine candidate. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:51 (abstract no. 29) Marovich M, Mascola J, Louder M, Eller M, Limbach K, El Habib R, Caudrelier P, Robb M, McNeil J, Birx D, Frankel S; US Military HIV Res Program, Rockville, MD. Recombinant canarypox virus (CP) vectors encoding HIV-1 genes are promising vaccine candidates inducing modest (approximately 40%) CTL responses in vaccinees. Based on prior data using DC to deliver immunogens, we postulate that direct ex vivo targeting of human dendritic cells (DC) could enhance the ... |
| 30 | HIV-1 gag-CTL epitope mapping in clade A/E infected Thai patients. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:51 (abstract no. 30) Ruxrungtham K, Buranapraditkul S, Hansasutha P, Rowland-Jones S, Sirivichaykul S, Warachit P, Honda M, Phanuphak P; Chulalongkorn Univ, Bangkok, Thailand. Our previous study, using a Cr51 release classic CTL assay, has shown that HIV-1 gag is the most common antigen recognized by >90% of Thai patients infected by HIV-1 clade A/E. In addition, HIV-1 gag has a very high rate of cross-clade CTL activity between clade A and B among clade A/E infected Thai ... |
| Session 7 — Symposium Drug Transports |
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| S1 | Role of P-glycoprotein in CNS and genital tract penetration. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:280 (abstract no. S1) Kim R; Vanderbilt Univ Sch of Med, Nashville, TN. HIV protease inhibitors have proven remarkably effective in treating HIV-1 infection. However, some tissues such as the brain and testes (sanctuary sites) are possibly protected from exposure to HIV protease inhibitors (HIV-PIs) due to drug entry being limited by the membrane efflux transporter P-glycoprotein ... |
| S2 | Effect of multidrug-resistance associated protein 4 on antiviral nucleotide analogs. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:280 (abstract no. S2) Fridland A; Gilead Sciences, Boulder, CO. We have identified and characterized a novel member of the ATP binding cassette superfamily of transport proteins (MRP) that interacts with nucleotide analogs. The MRPs are organic anion transporters that can mediate the cellular extrusion of many structurally unrelated drugs and are an important defense mechanism ... |
| S3 | Potential clinical relevance of drug transporters in antiretroviral pharmacology. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:281 (abstract no. S3) Back D, Jones K, Hennessy M, Khoo S, Meaden R, Mulcahy F, Barry M; Univ of Liverpool, UK. Penetration of antiretrovirals into all HIV-infected cells and compartments at concentrations sufficient for antiviral effect is essential if drugs are to effectively inhibit replication and prevent re- emergence of virus in plasma. P-glycoprotein (P-gp ) and multidrug resistance protein (MRP1) can actively extrude ... |
| S4 | Role of multidrug transporters in HIV pathogenesis. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:281 (abstract no. S4) Flexner C, Speck RR; Johns Hopkins Univ, Baltimore, MD. P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) are members of a class of highly conserved inducible transmembrane ATP-binding transporters; their physiologic function is poorly understood. Over-expression of these transporters is associated with cellular efflux of a variety of drugs. |
| Session 8 — Symposium HIV Vaccine Development |
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| S5 | Induction of mucosal CTL and their role in resistance against viral transmission. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:281 (abstract no. S5) Belyakov IM, Hel Z, Kelsall B, Ahlers JD, Nacsa J, Watkins DI, Allen TM, Sette A, Altman J, Woodward R, Markham P, Clements JD, Kuznetsov VA, Earl P, Moss B, Franchini G, Strober W, Berzofsky JA; NCI, NIH, Bethesda, MD. We have examined the role of CTL induced by mucosal vaccines in protection against mucosal transmission of viruses in a murine model and in an SHIV-macaque model. Mice immunized intrarectally with a peptide HIV vaccine containing helper and CTL epitopes produced CTL in the Peyer s patches and lamina propria of the ... |
| S6 | Mucosal T-cell immunity in HIV-1 infection and vaccination. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:281 (abstract no. S6) McElrath MJ; Fred Hutchinson Cancer Res Ctr, Seattle, WA. Acquisition of HIV-1 infection occurs predominantly by sexual transmission. The factors essential for the prevention or control of HIV-1 infection in the mucosa are not well understood. Mucosal T cells may provide an important immune defense against local infection. Our studies demonstrate that HIV-1-specific ... |
| S7 | The biology of alphavirus vectors and their use as vaccines for HIV. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:282 (abstract no. S7) Johnston RE; Univ of North Carolina, Chapel Hill. An expression system based on the alphavirus Venezuelan equine encephalitis virus (VEE) has been constructed. The RNA genome of VEE, in the form of a cDNA clone, is modified by substituting a gene of interest for the genes encoding the capsid and two glycoproteins which form the virion structure. In vitro transcripts ... |
| S8 | DNA-MVA/HIVA: A candidate HIV vaccine for Kenya. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:282 (abstract no. S8) Hanke T; Inst Molecular Med, Oxford, UK. Human immunodeficiency virus, the causative agent of AIDS, continues to spread throughout the world at an alarming rate. Development of a safe, efficient, affordable preventative HIV vaccine is the best hope for a long-term control of this pandemics. Using recent advances in biological and medical sciences, a novel ... |
| Session 9 — Slide Session and State-of-the-Art Lecture Co-Pathogens and Opportunistic Infections |
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| 31 | Pathogenesis of CMV immune recovery uveitis. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:52 (abstract no. 31) Schrier RD, Song MK, Karavellas M, Freeman WR, Durand D, Torriani FJ; Univ of California, San Diego. Successful control of HIV has literally provided a new lease on life for many infected patients who developed CMV retinitis prior to initiation of HAART. However, immune reconstitution in over half of treated retinitis patients has been accompanied at our institution by a debilitating ocular inflammation ... |
| 32 | Pharmacokinetic interactions between rifampin and efavirenz in patients with tuberculosis and HIV infection. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:52 (abstract no. 32) Lopez-Cortes LF, Ruiz R, Viciana P, Alarcon A, Leon E, Sarasa M, Lopez-Pua Y, Gomez J, Pachon J; Hosp Virgen del Rocio, Sevilla. Different therapeutic options have been recommended for the treatment of tuberculosis in HIV-infected patients; however, pharmacokinetic data for these combinations are very limited. Moreover, antituberculous treatment must ideally be given as fixed combinations. Our objective was to evaluate the ... |
| 33 | Amphotericin B lipid complex vs meglumine antimoniate in the treatment of visceral leishmaniasis in HIV-infected patients: a multicenter, open label, blinded, randomization, parallel controlled clinical trial. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:53 (abstract no. 33) Laguna F, Videla S, Jimenez-Mejias E, Sirera G, Torres-Cisneros J, Ribera E, Alvar J; Ctr Natl de Investigacion Clin, Madrid. Visceral leishmaniasis (VL) is common in patients with HIV infection living in endemic areas, but the most effective and safe treatment remains unknown. The aim of this study was to compare the efficacy and safety of amphotericin B lipid complex (ABLC) versus meglumine antimoniate (MA) in HIV-infected ... |
| 34 | Effect of HCV coinfection on HIV disease progression and survival in HIV-infected adults. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:53 (abstract no. 34) Sulkowski M, Moore R, Mehta S, Thomas D; Johns Hopkins Univ Sch of Med, Baltimore, MD. Chronic HCV infection acts as an OI in HIV-infected persons, since both its incidence and the severity of HCV-related liver disease are increased. However, the reverse impact, namely, the effect of chronic HCV infection on the natural history of HIV disease, is less certain. The objective of this study ... |
| 35 | Hepatitis C virus (HCV) clearance, viral load (VL) and alanine aminotransferase (ALT) levels in HIV-infected and uninfected hemophiliacs. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:53 (abstract no. 35) Daar ES, Lynn H, Donfield S, Gomperts ED, Hilgartner MW, Hoots WK, Chernoff D, Arkin S, Wong WY, Winkler C; Cedars-Sinai Med Ctr/Univ of California, Los Angeles. Little is known regarding the determinants of HCV clearance, vl, and ALT levels in HIV-infected and uninfected individuals. Methods: We studied 207 HIV-infected and 121 uninfected hemophiliacs with HCV infection who in 1989-1990 enrolled in the Hemophilia Growth and Development Study. CD4+ cells, ... |
| 36 | An open label pilot study of the safety and efficacy of adefovir dipivoxil in HIV/HBV co-infected patients with lamivudine resistant HBV. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:54 (abstract no. 36) Benhamou Y, Bochet M, Thibault V, Calvez V, Vig P, Brosgart C, Fry J, Poynard T, Katlama C; Hosp Pitie-Salpetriere, Paris, France. Lamivudine resistance (LAM(R)) to HBV occurs in approximately 15%-32% of both immunocompetent HBV- and HIV-infected patients after one year of lamivudine (LAM) therapy. The four year incidence of LAM(R) HBV is 90% in HIV/HBV co-infected patients treated with antiretroviral therapy containing LAM. |
| Session 10 — Poster Dendritic Cells, NK Cells, and γδ T-Cells |
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| 37 | Primary HIV-specific immune responses generated in vitro after priming with dendritic cells (DC) that have engulfed HIV-1-containing apoptotic bodies. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:54 (abstract no. 37) Spetz AL, Lore K, Rolen U, Flener Z, Holmgren L, Patterson BK, Andersson J; Karolinska Inst, Stockholm, Sweden. DC activates naïve T cells and efficiently presents antigens contained in apoptotic bodies. We have previously shown horizontal transfer of EBV-DNA and HIV-DNA by the uptake of apoptotic bodies in phagocytic cells. Virus-independent transfer of HIV-DNA by uptake of apoptotic bodies was demonstrated in human ... |
| 38 | Characterisation of in vitro derived dermal dendritic cells and Langerhans type cells for transduction with adenovirus vectors encoding HIV-1 clade C epitopes. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:54 (abstract no. 38) Perumal D, Roberts ML, Gilmour J, Dickson JG, Gotch F, Patterson S; ICSM. Dendritic cells (DCs) play a central role in controlling immunity. In vitro derived DCs have been used to map CTL epitopes in uninfected individuals. These cells are proving successful as an adjuvant in experiment cancer vaccines and may be a route of stimulating specific T cells in HIV infected individuals ... |
| 39 | Characterization of myeloid and lymphoid blood dendritic cell subsets in HIV-infected individuals. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:55 (abstract no. 39) Barron MA, Blyveis N, Martin K, Wilson CC; Univ of Colorado Hlth Sci Ctr, Denver. Dendritic cells (DCs) are potent antigen-presenting cells that activate CD4+ and CD8+ T lymphocytes. Blood DCs, characterized by the absence of lineage markers and expression of HLA- DR, can be subcategorized into two functional subsets. Myeloid DCs, or DC1 (CD11c+ DR+ Lin-), preferentially stimulate Th1 ... |
| 40 | Can anti-retroviral therapy restore the dendritic cell numbers in HIV-1-infected patients? Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:55 (abstract no. 40) Donaghy H, Qasi N, Pozniak A, Gazzard B, Nelson M, Imami N, Gotch F, Patterson S; Imperial Coll Sch of Med. Dendritic cells (DC) are potent antigen presenting cells which are essential for the initiation of primary immune responses but which are severely depleted in HIV infection. This study analyses the recovery of blood DC numbers in patients undergoing anti-retroviral therapy. Methods: Blood samples were ... |
| 41 | Substance P antagonist (CP96,345) inhibits HIV replication in human mononuclear phagocytes. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:55 (abstract no. 41) Lai JP, Ho WZ, Zhan GX, Yi Y, Collman RG, Douglas SD; Children's Hosp of Philadelphia. Substance P (SP) is a potent modulator of neuroimmunoregulation. SP affects macrophage function in an autocrine manner. SP-NK-1R interaction is an important trigger of intracellular events and may be involved in modulation of HIV infection of human MDM. We investigated the hypothesis that interruption of ... |
| 42 | Acute infection of myeloid cells with HIV-1 alters transcription factor binding to the IL-12 promoter. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:56 (abstract no. 42) Chambers KA, Angel JB; Ottawa Hosp Res Inst, Ontario, Canada. Impaired cell-mediated immunity (CMI) observed in HIV infection is paralleled by decreased production of IL-12, a cytokine crucial to development of CMI and defense against a variety of pathogens. Here we examine whether suppression of IL-12 expression is a consequence of direct cellular infection and ... |
| 43 | Altered natural killer (NK) receptor expression is restored with antiretroviral therapy and can be induced in vitro by IL-10. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:56 (abstract no. 43) Parato KG, Young CD, Angel JB; Ottawa Hosp Res Inst, Univ of Ottawa, Ontario, Canada. Normalization of NK cell function occurs in patients on effective antiretroviral therapy (ART) (K. Parato et al., CROI, 200). Since NK function is in part regulated by NK receptor expression, this suggests that NK receptor expression may be influenced by viral replication. Altered cytokine production that ... |
| 44 | Abnormalities in gammadelta T cells persist in HIV-1-infected individuals despite prolonged treatment with HAART. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:56 (abstract no. 44) Zhang L, Yu W, Guo Y, Yu J, Kim A, He T, Irvin C, Talal A, Markowitz M, Ho DD; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY. Significant alterations in gammadelta T-cell composition in the peripheral blood of HIV-1-infected individuals have been described. Methods and Results: To study the impact of therapy on these abnormalities, blood samples were collected from 48 patients, including longitudinal samples from 8 patients ... |
| 45 | Sequence variation in an 8.1-kb region of the human CCR5 gene. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:57 (abstract no. 45) Liu H, Nakayama EE, Xin X, Kawana-Tachikawa A, Goto M, Taguchi H, Yamada T, Takebe Y, Nakamura T, Nagai Y, Iwamoto A, Shioda T; Res Inst for Microbial Diseases, Osaka Univ. Mutations in the genes of HIV-1 coreceptors and their natural ligands have been shown to affect HIV-1 disease progression differently in different ethnic groups. The goals of this study were to gain a better understanding of the type and amount of CCR5 sequence variation and to establish the basis for ... |
| 45B | Polymorphisms in CCR2, CCR5, and HLA class I genes influence the course of HIV-1 infection in Rwandans as in Caucasians. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:57 (abstract no. 45B) Kaslow RA, Tang J, Naik E, Karita E, Allen S; Univ of Alabama at Birmingham. Polymorphisms in CCR2, CCR5 and HLA class I genes affect the course of HIV-1 infection but could do so differently in Caucasians and Africans because of distinctive genetic background, HIV-1 subtypes and other host and environmental factors. We evaluated relationships of these genes to disease progression i |
| 46 | CCR5 promoter and open reading frame polymorphisms affect in vitro susceptibility to infection with X4-tropic HIV-1. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:57 (abstract no. 46) Salkowitz JR, Zimmerman PA, Meyerson HJ, Mosier DE, Lederman MM; Case Western Reserve Univ, Cleveland, OH. Our objective was to explore the relationship between CCR5 ORF (delta 32) and promoter (CCR5 59029-A or -G) polymorphisms and in vitro infection with the R5-tropic (JR-FL) and the X4-tropic (NL4-3) strains of HIV-1. Methods: PBMC of HIV-uninfected individuals were infected after near optimal and suboptimal ... |
| 47 | HIV-1 infection of macrophages induces production of platelet activating chemokines. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:58 (abstract no. 47) Olivieri KC, Suttitanamongkol S, Polanowska-Grabowska RK, Gear AR, Camerini D; Univ of Virginia Hlth Sci Ctr, Charlottesville. Thrombocytopenia (TP) occurs in as many as 40% of patients infected with HIV-1. Currently there is no well characterized mechanism to explain this phenomenon. In some cases of HIV-1 associated thrombocytopenia, anti-platelet antibodies have been isolated. These antibodies might be responsible for the platel ... |
| 48 | Inhibition of chemokine-directed megakaryocyte migration by HIV-1: a new mechanism for HIV- associated thrombocytopenia. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:58 (abstract no. 48) Domenech FN, Rafii S, Fakruddin MJ, Lane W, Zlatopolskiy A, Laurence J; Weill Med Coll of Cornell Univ, New York, NY. Current pathophysiologic models of human immunodeficiency virus (HIV)-associated thrombocytopenia purpura are based upon those of idiopathic immune thrombocytopenic purpura (ITP). However, ITP is characterized by immunologic destruction of platelets, which is not characteristic of many patients with HIV-... |
| 49 | Differential CD4/CCR5 utilization, conformation and neutralization sensitivity between envelopes from a microglia-adapted HIV-1 and its parental isolate. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:58 (abstract no. 49) Martin J, Labranche C, Gonzalez-Scarano F; Univ of Pennsylvania Sch of Med, Philadelphia. A primary isolate (HIV-1 BORI was sequentially passaged in cultured microglia. The isolate recovered (HIV-1 BORI-15 replicated efficiently in microglia and was highly fusogenic (J. Virol. 70: 7654). The syncytium-inducing phenotype was associated with 4 amino acid differences in the V1/V2 region of gp120, ... |
| 50 | CXCR4 mediates both survival and death prone signals in primary human CD4 T cells. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:58 (abstract no. 50) Vlahakis S, Bou G, Heppelmann C, Paya CV; Mayo Clin, Rochester, MN. Chemokine receptors play a key role in chemotaxis and also serve as co-receptors for HIV. CXCR4, when bound by its natural ligand, stromal derived factor (SDF), triggers cell chemotaxis, whereas when bound by X4 env it results in cell death. To understand this dichotomy of CXCR4 receptor function we have ... |
| 51 | "Resistance factors" in highly exposed persistently seronegative (HEPS) women married to HIV- infected men in Chiang Mai, Thailand. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:59 (abstract no. 51) Duerr A, Costello C, Suriyanon V, Robison V; CDC, Atlanta, GA. Factors associated with apparent HIV resistance are most often studied in commercial sex workers whose true exposure to HIV is unknown. We studied resistance in women, who had exposure to a single partner, selected from a couples study of HIV-infected (HIV+) Thai male blood donors and their wives. |
| 52 | Genetic, virological and immunological characterization of a cohort of long-term monogamous HIV discordant couples. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:59 (abstract no. 52) Braganza R, Beddows S, Frazeo S, Dong T, Rostron T, Rowland-Jones S, Weber J, Fidler S; Imperial Coll Sch of Med at St Mary's, London, UK. There is increasing evidence of HIV-1-specific immune responses in individuals who despite frequent HIV-1 sexual exposure remain seronegative (ESN). Much of this work has focused on a cohort of seronegative prostitutes in Nairobi exposed to different sources of HIV. Here we define a cohort of monogamous ... |
| 53 | HIV-1-specific cellular responses in HIV-1 discordant couples. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:59 (abstract no. 53) Pinheiro SF, Dong T, Rostron T, Fidler S, Tamm N, Weber J, McMichael A, Rowland-Jones S; Inst of Molecular Med, Oxford. Individuals who remain seronegative despite repeated exposure to HIV infection could provide clues in understanding protection from HIV infection. There is increasing evidence that many individuals with documented exposure to HIV who remain seronegative generate HIV-specific cellular immune responses. |
| 54 | Pet imaging of the immune response to HIV. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:60 (abstract no. 54) Iyengar S, Chin B, Sabundayo B, Quinn T, Margolick J, Schwartz D; Johns Hopkins Univ, Baltimore, MD. Lymphocyte activation can be detected in vivo with radiolabeled glucose analogs by positron emission tomography (PET). Scharko et al. (PNAS 93: 6425,1996) showed progressive systemic lymph node involvement in monkeys infected with a pathogenic SIV. We document, in humans, a pattern of HIV induced node ... |
| 55 | Evaluation of immune activation in HIV-infected and -uninfected African individuals by single-cell analysis of cytokine production. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:60 (abstract no. 55) Rizzardini G, Trabattoni D, Declich S, Lukwiya M, Piconi S, Clerici M; Milano, Italy. Backgound: Immune activation is reported to be common in both HIV-infected and -uninfected African individuals. This activation is probably secondary to environmental reasons and is suggested to result in profound modifications of the interaction between the immune system and HIV. To better characterize immune ... |
| 56 | Reduced activation and apoptosis of peripheral CD3+/CD4+ T cells persists after viral rebound in AIDS patients treated with mycophenolate mofetil (MMF). Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:60 (abstract no. 56) Coull JJ, Margolis DM; Univ of Texas Southwestern Med Ctr at Dallas. Mycophenolate Mofetil, used as an immunosuppressant in transplantation, is hydrolyzed after oral absorption to mycophenolic acid (MPA). As little as 125 nM MPA has significant antiviral activity in vitro, but 2 micromolar MPA has been reported to induce apoptosis in activated PBMCs. A cohort of patients ... |
| 57 | Survival of transfused donor white cells in HIV-infected recipients. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:61 (abstract no. 57) Kruskall MS, Lee TH, Assmann SF, Laycock ME, Kalish LA, Lederman MM, Busch MP; Beth Israel Deaconess Med Ctr, Boston, MA. The appearance and expansion of donor white blood cells (WBC) in a recipient post- transfusion has many potential biological ramifications. Although HIV-infected individuals are ostensibly at high risk for microchimerism (MC), transfusion-associated graft-versus-host disease (TA-GvHD) is extremely rare. |
| 58 | CD4+ T lymphocyte activation and shift from naïve to effector/memory phenotype after HTLV-I infection and HTLV-I associated myelopathy. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:61 (abstract no. 58) Santos MD, Biasutti C, Segurado AC, Casseb J, Salomao R, Kallas EG; Federal Univ of Sao Paulo. Even though human T-cell lymphotropic virus type I (HTLV-I) infection is usually asymptomatic, HTLV-I carriers can develop diseases, mainly adult T-cell leukemia- lymphoma or HTLV-I-associated myelopathy (HAM). To date, limited immunophenotyping data in HTLV-I infection and non-hematological related ... |
| 59 | Human anti-HIV-1 monoclonal antibodies that completely prevent SHIV infection of rhesus monkeys have potent, synergistic ADCC activity. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:61 (abstract no. 59) Zahr EA, Lainwala S, Baba TW; Floating Hosp for Children at New England Med Ctr. Passive immunization of neonatal or adult rhesus macaques with the triple combination of human anti-HIV-1 neutralizing mAbs (F105, 2G12, 2F5) completely protected them from oral or i.v. simian/human immunodeficiency virus (SHIV) challenge (Baba et al., 2000). The mechanism(s) of protection is unknown. |
| 60 | Use of transgenic mice for the efficient isolation of novel human monoclonal antibodies with neutralizing activity against primary HIV-1 strains. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:61 (abstract no. 60) He Y, Honnen W, Krachmarov C, Burkhart M, Kayman S, Corvalon J, Pinter A; Pub Hlth Res Inst, New York, NY. Despite considerable interest in developing clinically useful monoclonal antibodies (Mabs) against HIV-1, very few such Mabs have been identified. Human antibodies (HuMabs) are preferred over rodent Mabs for clinical applications, but isolation of HuMabs by standard methods of EBV transformation of B cells ... |
| 61 | Additive effects characterize the interaction of most antibodies involved in HIV-1 primary isolate neutralization. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:62 (abstract no. 61) Verrier F, Nadas A, Gorny MK, Zolla-Pazner S; New York VA Med Ctr. Human immunodeficiency virus-type I (HIV-1) infection elicits antibodies directed against several regions of the gp120 and gp41 envelope glycoproteins. Many of these antibodies are able to neutralize T cell line-adapted strains (TCLA) of HIV-1, but only a few effectively neutralize primary HIV-1 isolates. |
| 62 | A human single-chain antibody to gp41 of human immunodeficiency virus type 1 (HIV-1). Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:62 (abstract no. 62) Liu F, Ma Q, Junghans R, Posner M, Cavacini L; Beth Israel Deaconess Med Ctr, Boston, MA. The transmembrane ENV protein of HIV-1, gp41, plays a crucial role in the early step of virus entry into target cell. This property and the lower genetic variability of gp41 among HIV-1 clades suggest that it may be a target of choice to design a specific molecule for HIV-1 molecular immunotherapy. |
| 63 | Evolution of plasma levels of soluble interleukin-2 (sIL2-R) and tumor necrosis factor type II (sTNFII-R) receptors is correlated with immunologic or virologic responses of patients treated by protease inhibitor- containing regimen. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:62 (abstract no. 63) Bonnet F, Saves M, Morlat P, Droz C, Peuchant E, Pellegrin I, Bonarek M, Bernard N, Lacoste D, Beylot J, Chene G; Saint-Andre Hosp. The prognostic value of plasma markers of immune activation had been demonstrated before the era of HAART but has been poorly studied since then. Methods: 46 protease inhibitor (PI)-naïve HIV-1-infected adults were consecutively included in a one-year prospective cohort from the initiation of a PI-containin ... |
| 64 | Actinomycin D enhances HIV-1 replication via an interleukin-9 dependent mechanism. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:62 (abstract no. 64) Imamichi T, Berg SC, Lempick RA, Palmer LD, Baseler MW, Adelsberger JW, Watkins CM, Murphy MA, Nelson EL, Prieto DA, Guo J, Levin JG, Lane HC; SAIC-Frederick/NCI-FCRDC, Frederick. Actinomycin D (ActD), a transcription inhibitor, has been reported as a potential suppressor of HIV-1 replication. In this study, we evaluated the impact of ActD on HIV replication in tissue culture. Methods: MT-2, MT-4, and Jurkat cells and PBMC were infected with a wild-type HIV-1, NL4.3, and then culture ... |
| 65 | Interleukin-12 (IL-12) augmentation of T-cell proliferation of HIV+ PBMC is mediated via IL-12 receptor upregulation. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:63 (abstract no. 65) Benson EM, Jones ML, Puls R, Young JM, Huang QR; Westmead Hosp/Sydney Univ, Australia. A number of studies have demonstrated that recombinant human (rh) IL-12 augments antigen-specific T-cell proliferation and cytokine secretion by PBMC from patients with HIV infection. Our own data in this regard suggest that the augmentation of proliferation of PBMC from HIV+ individuals might be greater ... |
| 66 | Effect of recombinant human soluble tumor necrosis factor receptor (TNFR, etanercept) on interleukin-6 (IL-6), TNF-α, and markers of immune activation in HIV-infected subjects receiving interleukin-2 (IL-2). Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:63 (abstract no. 66) Sha B, Valdez H, Landay A, Gelman R, Namkung A, Agosti J, Bancroft L, Mildvan D, Mitsuyasu R, Pollard R, Ogata-Arakaki D, Kilgo P, Estep S, Fox L, Lederman M; Rush Med Coll, Chicago, IL. Neutralization of circulating TNF-α may block IL-2 induced activation of proinflammatory cytokine expression. Methods: A prospective, open-label, completed trial of HAART, HAART + SC IL-2 (7.5 MIU bid 5d q8wks), or HAART + continuous IV (CIV) IL-2 (9 MIU qd 5d q8wks). Plasma IL-6, IL-4, IL-10, IL-12, IF ... |
| 67 | SDF-1 anti-HIV-1 fusogenic activity is mediated by complexing with heparan sulfate proteoglycans. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:63 (abstract no. 67) Valenzuela Fernandez A, Palanche T, Magerus A, Altmeyer R, Virelizier JL, Baleux F, Galzi JL, Arenzana-Seisdedos F; Inst Pasteur, Paris. The chemokine CXCL12 or SDF-1 inhibits CXCR4-mediated HIV infection (X4 HIV strains) of CD4+ T lymphocytes, macrophages and dendritic cells. The biological functions of chemokines are thought to be influenced by their association with cellular or matrix extracellular glycosaminoglycans (GAGs). We recently ... |
| 68 | CCR5 expression, CC-chemokine production and viral isolation in HIV-infected individuals receiving HAART or HAART + IL-2. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:64 (abstract no. 68) Oliva A, Kinter A, Rabin R, Metcalf J, Moir S, Malaspina A, Lane HC, Fauci AS; IRCCS L Spallanzani, Rome, Italy. CC-chemokines and the HIV coreceptor CCR5 play a pivotal role in HIV pathogenesis. It has been shown that IL-2 modulates the expression of these molecules, but the link between IL-2, chemokines, coreceptors and viral isolation in patients receiving IL-2 is not yet fully understood. Methods: 12 HIV-infected ... |
| 69 | Deregulation of the expression of the fractalkine/fractalkine receptor complex in HIV-infected patients. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:64 (abstract no. 69) Foussat A, Boucher-Delbos L, Berrebi D, Krzysiek R, Galanaud P, Levy Y, Emilie D; Inst Paris-Sud sur les Cytokines, Clamart. Fractalkine (FKN) is the only member of the CX3C chemokine family. Polymorphism of the fractalkine receptor (CX3CR1) gene influences the prognosis of HIV infection. To gain insight into the mechanism of this effect on prognosis, expression of FKN and of its receptor was analyzed in HIV-infected patients. |
| 70 | Regulation of cytokines and chemokines by HIV, Tat, and gp120 in astrocytes. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:64 (abstract no. 70) Galey D, Woodward J, Nath A; Univ of Kentucky, Lexington. Cytokines and chemokines have been implicated in a multifaceted way in neurological complications associated with human immunodeficiency virus type 1 (HIV-1). Given the large number of astrocytes in the CNS, we hypothesized that they may have a key role in the production of cytokines and chemokines. |
| 71 | HIV and SIV gp160/120 envelope glycoproteins induce upregulation of B7-1 and B7-2 on antigen- presenting cells. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:64 (abstract no. 71) Rubbert A, Arthos J, Cicala C, Machado E, Fox C, Passon D, Fauci AS; NIAID, NIH, Bethesda, MD. The interaction of antigen-presenting cells and T cells within lymphoid tissue, and especially dendritic cells, has been implicated in activation of T cells, transmission of virus and initiation of replication. Expression of B7-1 and B7-2 on antigen-presenting cells and interaction with CD28 on T cells are ... |
| 72 | HIV-1 gp120 enhances expression of CD40 and co-stimulatory molecules on dendritic cells, priming them to stimulate T-cell lymphoproliferation. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:65 (abstract no. 72) Williams MA, Spector SA; Univ of California, San Diego. Immune activation requires antigen specific CD4+ T(H) cells to aid in priming of CD8+ CTL that is optimal when T(H) and CTL recognize antigen presented by a dendritic cell (DC). In this research, we hypothesized that DC exposed to HIV-1 gp120 would exhibit altered T-cell co- stimulatory capacity. |
| 73 | Programmed cell death regulation by HIV-1 envelope glycoprotein gp120 and the chemokine SDF-1 alpha in human B lymphocytes. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:65 (abstract no. 73) Patke C, Shearer W; Baylor Coll of Medicine. HIV-1 infection results in abnormalities of B cell function. The dysfunction in the B cell population of HIV-1 infected individuals may be paralleled by priming of B cells for apoptotic cell death. To evaluate the possible relevance of this event to HIV pathogenesis and disease progression, regulation of B ... |
| 74 | Recombinant HIV-1 gp120 induces distinct types of delayed hypersensitivity in persons with or without pre-existing immunologic memory. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:65 (abstract no. 74) Hladik F, Bender S, Akridge R, Hu Y, Galloway C, Francis D, McElrath J, Hu C; Fred Hutchinson Cancer Res Ctr, Seattle, WA. Induction of T-cell help is critical in HIV-1 control and potentially in prevention by immunization. A practical approach is needed to identify HIV-1-specific helper activities in vivo. Methods: We explored the feasibility of inducing delayed-type hypersensitivity (DTH) following intradermal injection of ... |
| 75 | Role of proinflammatory mediators and CD11a-ligand interactions in HIV-1 infected macrophage transmigration across an activated HEC-1 cell monolayer. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:65 (abstract no. 75) Carreno MP, Chomont N, Hocini H, Eirinopoulou T, Krief C, Kazatchkine MD, Belec L; Inst Natl de la Sante et de la Res Med, Paris, France. Most HIV-positive patients have been infected during heterosexual contact, implying that the virus must breach the protective epithelial barrier that lines the human genital tracts. We have used confluent monolayers of cultured human endometrial carcinoma (HEC-1 cells) to model mucosal genital epithelium. |
| 76 | T lymphocytes in the cervix of normal women show high levels of activation markers and increased levels of CCR5 receptor expression in women taking the combined oral contraceptive. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:66 (abstract no. 76) Prakash M, Kapembwa M, Gotch F, Patterson S; Imperial Coll, London. Heterosexual transmission is the predominant route of HIV infection. Most research, however, has focused on the blood rather than the genital tract. The female genital tract is the site where infection is initiated and where virus can be transmitted to a new host. In addition to infection, combined oral ... |
| 77 | R5 but not X4 HIV strains kill primary CD4+ T cells through the fas signaling pathway. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:66 (abstract no. 77) Algeciras-Schimnich A, Vlahakis SR, Heppelmann CJ, Paya CV; Mayo Clin, Rochester, MN. While apoptosis of both HIV infected and uninfected CD4+ T cells is implicated in T cell depletion, the molecular mechanism mediating apoptotic death is controversial. While some groups argue for Fas/FasL and hence caspase mediated death, others conclude that it is caspase independent. Based on studies from |
| 78 | Characterisation of the CD4 Th1 and CD8 responses against hepatitis C virus and HIV in peripheral blood of HCV-HIV coinfected patients. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:66 (abstract no. 78) Alatrakchi N, Di Martino V, Thibault V, Bochet M, Katlama C, Poynard T, Autran B; Hosp Pitie-Salpetriere, Paris, France. The frequency of HIV and HCV coinfections led us to analyze the T cell responses against both viruses and to investigate the consequences of the HIV related immune defects for the HCV-specific T cell responses. Methods: Three groups were studied: 1) long term nonprogressors (LT-NP) (n = 12), 2) coinfected p |
| 79 | Extrahepatic manifestation of hepatitis C in patients coinfected with HIV. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:66 (abstract no. 79) Woitas RP, Rockstroh JK, Bockemuehl R, Schepers K, Stoschus B, Brackmann HH, Matz B, Sauerbruch T, Spengler U; Univ of Bonn, Germany. Hepatitis C virus (HCV) infection, which is frequent in HIV patients, can cause multiple extrahepatic manifestations such as autoantibody formation or cryoglobulinemia. It is unclear as to how far immunodeficiency associated with HIV infection affects these extrahepatic manifestations of HCV infection, whic |
| 80 | Non-proliferating bystander CD4+ T cells lacking activation markers support HIV replication during immune activation in a lymphoid environment. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:67 (abstract no. 80) Scales D, Ni H, Shaheen F, Capodici J, Cannon G, Weissman D; Univ of Pennsylvania Sch of Med, Philadelphia. It is generally accepted that HIV replicates in proliferating CD4+ T cells and non- proliferating dendritic cells (DC) and macrophages based on in vitro studies of cells isolated from peripheral blood. However, in infected individuals, HIV predominantly replicates in the paracortical region of lymphoid orga |
| 81 | Env is a cytopathic determinant of R5-AIDS HIV-1 in SCID-hu mice; nef may also be involved. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:67 (abstract no. 81) Scoggins RM, Brodrick B, Calvert M, Taylor Jr JR, Camerini D; Univ of Virginia, Charlottesville. We recently reported that AIDS-associated R5 HIV-1 (R5-AIDS) biological clones have greater cytopathic effects on CD4+ thymocytes and replicate to higher levels than pre-AIDS R5 biological clones in SCID mice bearing human thymus liver grafts (SCID-hu mice). Methods: To map these phenotypes, we isolated the |
| 82 | Induction of a cellular factor during HIV-1 infection that modulates surface CD4 expression. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:67 (abstract no. 82) Sheeter D, Rought S, Du P, Peay J, Vicenzi E, Richman D, Gingeras T, Corbeil J; Univ of California, San Diego, La Jolla. Large scale monitoring of gene expression has led to a new discovery-driven paradigm in the study of complex biological systems. Methods and Results: We have identified a number of new host cell genes putatively associated with HIV pathogenesis that are modulated in both CD4+ T cell lines and primary CD4+ T |
| 83 | Transmitted multi-drug resistant (MDR) HIV-1: virologic and immunologic characterization during and after treatment. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:68 (abstract no. 83) Simon V, Vanderhoeven J, Ortiz GM, Sheehy ME, Hurley A, Jin X, Deschenes G, Dawson K, Parkin N, Nixon DF, Markowitz M; Aaron Diamond AIDS Res Ctr, New York, NY. It has been observed that a significant number of subjects harboring MDR HIV-1 may maintain lower levels of plasma HIV-1 RNA when compared to pre-treatment levels. It has been hypothesized that this may reflect altered fitness of the MDR variant. Here we characterize the virologic and immunologic course of |
| 84 | The second exon of SIVmac239 tat contributes to chronic viral replication and disease. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:68 (abstract no. 84) Smith SM, Neuveut C, Marx PA, Jeang KT; St Michael's Med Ctr, Newark, NJ. The Tat proteins of HIV and SIV are encoded by two exons. The role of the second exon of HIV or SIV tat in pathogenesis has not been evaluated. To explore this issue, we constructed a clone (SIVtat1ex) of SIVmac239, which encodes for only the first exon of tat, and studied it in vivo. Methods: Sequential st |
| 85 | Novel evidence for protection of CD4+ T cells against cell killing by different HIV-1 strains in HIV- infected true non-progressors. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:68 (abstract no. 85) Wang B, Dyer W, Sullivan J, Zaunders K, Saksena NK; Westmead Millennium Inst, Westmead Hosp, Sydney, NSW. The actual biological, molecular and immunological reasons for non-progression in HIV-infected patients remain unclear. Methods and Results: Sequencing analysis of a unique HIV-1 infected long-term non-progressor (LTNP) with undetectable viral load and unculturable virus revealed no viral evolution in the p |
| 86 | R77Q mutation decreases the ability of Vpr to induce apoptosis. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:68 (abstract no. 86) Lum JJ, Cohen OJ, Pilon AA, Kim JE, Chen Z, Sanchez-Dardon J, Hawley-Foss N, Garber G, Fauci AS, Badley AD; Ottawa Hosp, Ontario, Canada. 25%-30% of long-term nonprogressors (LTNP) have mutations in CCR5 and CCR2, yet reasons for 75% of LTNP remain undefined. HIV-1 accessory proteins contribute to HIV disease; in particular, the C-terminal domain of Vpr is important for cell cycle arrest and apoptosis. We have evaluated mutations in the apopt |
| 87 | Transmission of specific antiviral resistance mutations within partner pairs. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:69 (abstract no. 87) Hecht FM, Kahn JO, Warmerdam M, Webb M, Digilio L, Lee KH, Grant RM; Univ of California, San Francisco. Preferential transmission of wild-type viral variants from persons with ZDV resistance mutations has been suggested from prior studies, implying that there may be selective pressure against transmission of some drug resistant HIV variants. We studied partner pairs to determine whether specific drug resistan |
| 88 | Analysis of viral nef alleles in women with non-progressive or slowly progressive HIV-1 infection. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:69 (abstract no. 88) Greenough T, Schwartz A, O'Reilly S, Somasundaran M, Sullivan J, Carpenter C, Flanigan T; Univ of Massachusetts Med Sch, Worcester. Gender differences may exist with respect to viral load and disease progression. Methods and Results: We have initiated studies to examine the role of viral determinants in non- progressive infection. We have studied three women with long-term non-progressive HIV-1 infection and three untreated women who ha |
| 89 | Acute infection of Asian macaques by a vaginally transmissible subtype-C, R5-tropic SHIV. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:69 (abstract no. 89) Chen Z, Zhao X, Huang Y, Gettie A, Blanchard J, Ho DD; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY. An R5-tropic SHIV(CHN19) was previously generated using a primary HIV-1 subtype-C envelope. The infectivity of SHIV(CHN19) in vivo was greatly enhanced after serial passages in pig-tailed macaques. Methods and Results: We have since further characterized this SHIV in two species of macaques. Despite inactiv |
| 90 | Phenotypic changes associated with mutations of pathogenic R5 SHIV. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:70 (abstract no. 90) Hsu M, Harouse J, Cheng-Mayer C; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY. To further define the role of human immunodeficiency virus type 1 (HIV-1) infection, a chimera of simian immunodeficiency virus (SIV) and the env gene of HIV-1(SF162) (SHIV162) was constructed. HIV- 1(SF162) is macrophage-tropic and non-cytopathic, and it uses the CCR5 entry co-factor. SHIV(SF162) establish |
| 91 | Increased fusogenicity and replicative capacity conferred by the extracellular envelope glycoprotein of pathogenic simian-human immunodeficiency virus SHIV-SF33A. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:70 (abstract no. 91) Chakrabarti LA, Ivanovic T, Cheng-Mayer C; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY. In vivo adaptation of the simian-human immunodeficiency virus clone SHIV-SF33 resulted in the emergence of the pathogenic isolate SHIV-SF33A, which caused a rapid and severe CD4+ T cell depletion when inoculated in rhesus macaques. Molecular clones were generated by cloning the env V1 to V5 region amplified |
| 92 | An SIV macaque model that more closely approximates HIV pathogenesis in humans. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:70 (abstract no. 92) Ling B, Veazey RS, Martin LN, Luckay A, Marx PA; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY. The predominant human immunodeficiency virus (HIV) models are simian immunodeficiency virus (SIV) and simian-human hybrid viruses in rhesus macaques of Indian origin (Ind Rh). The model has significant limitations; Ind Rh are in short supply, develop AIDS more rapidly than humans and have viral plasma loads |
| 93 | How important are viral peaks for SIV pathogenesis? Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:70 (abstract no. 93) Regoes RR, Staprans SI, Feinberg MB, Bonhoeffer S; Swiss Federal Inst of Technol, Zurich. The duration of HIV-1 infection, from transmission of the virus to death, is highly variable, ranging from two years up to decades. The mechanisms leading to AIDS and subsequently to death are not yet fully understood. However, correlates with accelerated progression to disease are available, such as CD4 ce |
| 94 | Quantitative analysis of SHIV replication in multiple tissues of rhesus macaques. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:71 (abstract no. 94) Pereboeva L, Komarova S, Rakasz E, Bucy P; Univ of Alabama at Birmingham. A key to understanding HIV pathogenesis is characterization of dynamics of viral replication in lymphoid tissue. Since the different lymphoid tissues have multiple distinct characteristics, but all may contribute to in vivo infection, we have performed quantitative analyses of both cellular and viral compon |
| 95 | Detection of viral RNA in CD4- CD8- and CD4- CD8+ lymphocytes in vivo in rhesus monkeys infected with simian immunodeficiency virus of macaques. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:71 (abstract no. 95) Benito Huete JM, Chatis PA, Schmitz JE, Kuroda MJ, Letvin NL, Reimann KA; Beth Israel Deaconess Med Ctr, Harvard Med Sch, Boston, MA. A definition of the specific cell types that support HIV replication early in the course of infection will be important for understanding AIDS pathogenesis and designing strategies for preventing infection. Recent observations have indicated that the population of lymphocytes susceptible to productive infec |
| 96 | The N-terminal v3 loop glycan modulates the interaction of clade A and B human immunodeficiency virus type 1 envelopes with CD4 and chemokine receptors. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:71 (abstract no. 96) Malenbaum S, Yang D, Cavacini L, Posner M, Robinson J, Cheng-Mayer C; Aaron Diamond AIDS Res Ctr, Rockefeller Univ, New York, NY. We previously reported that the presence of a conserved glycosylation site within the V3 loop of envelope gp120 rendered the pathogenic SHIV(SF33A) virus resistant to neutralization with HIV-1 sera. The epitope(s) that is shielded by the V3 loop glycan therefore appears to be shared between the X4 SHIV(SF33 |
| 97 | A biosensor assay for studying ligand-membrane receptor interactions: binding of antibodies and HIV-1 env to chemokine receptors. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:72 (abstract no. 97) Hoffman T, Canziani G, Jia L, Rucker J, Doms R; Univ of Pennsylvania, Philadelphia. The HIV envelope (Env) protein mediates entry into cells by binding CD4 and an appropriate coreceptor, which triggers structural changes in Env that lead to fusion between the viral and cellular membranes. The major HIV-1 coreceptors are the seven-transmembrane-domain chemokine receptors CCR5 and CXCR4. The |
| 98 | Differential use of human and rhesus CCR5 by a CD4-independent HIV-2 identifies contact residues between the envelope glycoprotein and the N-terminus of CCR5. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:72 (abstract no. 98) Lin G, Lee B, Haggarty B, Doms R, Hoxie J; Univ of Pennsylvania, Philadelphia. A variant of HIV-2/NIHz termed HIV-2/vcp infects a number of CD4-negative cell lines using CXCR4 as a primary receptor (Endres, M., et al., Cell 87, 1996). An env clone of HIV- 2/vcp was shown to mediate fusion on CXCR4-positive/CD4-negative QT6 quail cells. Understanding CD4-independent use of coreceptors |
| 99 | Antigenically distinct conformations of CXCR4. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:72 (abstract no. 99) Baribaud F, Sharron M, Brelot A, Price K, Alizon M, Broder CC, Tsang M, Doms RW; Univ of Pennsylvania, Philadelphia. The major human immunodeficiency virus type 1 (HIV-1) coreceptors are the chemokine receptors CCR5 and CXCR4. To a first approximation, the expression patterns of the major coreceptors, coupled with their use by HIV-1 strains, largely explain viral tropism at the level of entry. However, while virus infecti |
| 100 | HIV-1 gp120 and chemokines activate Pyk2 and map kinases in primary human macrophages. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:72 (abstract no. 100) Del Corno M, Liu QH, Freedman BD, Collman RG; Univ of Pennsylvania Sch of Med, Philadelphia. HIV-1 uses the chemokine receptors CCR5 and CXCR4 as coreceptors for entry into target cells. Engagement of these receptors by HIV-1 envelope glycoprotein is essential for membrane fusion and may additionally activate intracellular signaling pathways. We previously showed that the HIV-1 envelope gp120 (Env) |
| 101 | Replacement of V3 region of gp120 with endothelin-1 endows HIV-1 with CD4 independent infectivity. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:73 (abstract no. 101) Takaori-Kondo A, Hori T, Yonezawa A, Morita R, Uchiyama T; Graduate Sch of Med, Kyoto Univ, Japan. We have demonstrated that replacement of V3 region of gp120 with several loop peptide hormone ligands and cytokines such as endothelin-1 (ET-1) and SDF-1 preserves viral infectivity in cells expressing the corresponding receptors using pseudotyped viruses with the luciferase reporter gene, indicating that the ligand/re |
| 102 | Analysis of cytopathic effects of NSI and SI HIV-1 on different CD4+ T cell subsets in PHA- stimulated PBMC in vitro. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:73 (abstract no. 102) Kwa IS, Broersen S, Vingerhoed J, Zagwijn E, Schuitemaker H; CLB-Sanquin, Amsterdam, The Netherlands. SI and NSI isolates are equally cytopathic, but only for CD4 cells with membrane expression of the appropriate coreceptor. The depletion of truly naïve CD4 cells after SI infection is in agreement with the capacity of SI HIV- 1 to infect naïve CD4 cells in vivo. |
| 103 | HIV-1 envelope N-linked glycosylation patterns as a determinant of co-receptor usage and viral infectivity. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:73 (abstract no. 103) Pollakis G, Chalaby MI, Kliphuis A, Goudsmit J, Paxton WA; Univ of Amsterdam, The Netherlands. Both the V1-V2 and the V3 regions of the HIV-1 gp120 envelope have been implicated in influencing viral co-receptor usage. Many studies have reported on the significance of the V3 region charge with respect to viral phenotype and co-receptor usage patterns. Methods: We have generated and used a panel of ... |
| 104 | Palmitoylation-dependent microdomain localization of CCR5 and CD4 may affect HIV receptor functions. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:73 (abstract no. 104) Percherancier Y, Planchenault T, Virelizier JL, Arenzana-Seisdedos F, Bachelerie F; Inst Pasteur, Paris, France. Numerous studies indicate that glycosphyngolipids and cholesterol membrane-rich domains (rafts) have a major function in activation signal transmission. The uncontested localization of CD4 within rafts argues in favor of the existence of a functional complex of CD4 with HIV co- receptors within rafts. |
| 105 | Multimeric CD4 and coreceptor binding is required to activate HIV-1 envelope protein trimers. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:74 (abstract no. 105) Edwards T, McManus C, Richardson T, Girard Y, Hoffman T, Doms RW; Univ of Pennsylvania, Philadelphia. The trimeric HIV envelope protein (Env) mediates attachment of virus to the host cell surface and facilitates virus entry. The first step in this process is Env binding to CD4, which results in conformational changes in the gp120 subunit of Env. This interaction enables Env to subsequently interact with a c |
| 106 | HIV-1 coreceptor activity of CCR5/CXCR4 chimeras. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:74 (abstract no. 106) Pontow S, Ratner L; Washington Univ Sch of Med, St Louis, MO. The chemokine receptors CCR5 and CXCR4 are the primary coreceptors mediating entry of HIV-1 into CD4-positive cells. To study the determinants of coreceptor usage, we generated a set of chimeric HIV-1 coreceptors that express all possible combinations of the 4 extracellular domains of CCR5 and CXCR4. |
| 107 | Chemokine receptor usage by primary HIV-2 isolates: identification of two isolates unable to use any chemokine receptor to enter GHOST cells. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:74 (abstract no. 107) Azevedo-Pereira JM, Reeves J, Mansinho K, Santos-Costa Q, Clapham P, Moniz-Pereira J; Univ de Lisboa, Portugal. In primary HIV-1 isolates the utilization of CCR5 and CXCR4 coreceptors correlates with disease progression. Accordingly, CXCR4 usage is more frequent in isolates obtained from patients with immunodeficiency. In HIV-2, however, the patterns of coreceptor usage seemed more complex than for HIV-1, with an ... |
| 108 | Relationships between CD4 independence, neutralization sensitivity and exposure of a CD4-induced epitope in an HIV-1 envelope protein. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:74 (abstract no. 108) Edwards T, Hoffman T, Baribaud F, Romano J, Adkinson J, Wyss S, Sharron M, Doms RW, Hoxie JA; Univ of Pennsylvania, Philadelphia. A CD4-independent version of the X4 HIV-1 IIIB envelope (Env) protein, termed 8x, mediates infection of CD4-negative, CXCR4-positive cells, binds directly to CXCR4 in the absence of CD4 due to constitutive exposure of a conserved coreceptor binding site in the gp120 subunit, and is more sensitive to ... |
| 109 | Role of gp120 N-linked glycosylation in the CD4-independent tropism of the HIV-1 m7NDK virus. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:75 (abstract no. 109) Dumonceaux J, Joliot V, Briand P, Hazan U; INSERM Unite 380, Paris, France. HIV enters target cells upon binding of the envelope glycoprotein gp120 to CD4 and a co-receptor belonging to the seven-transmembrane G-coupled chemokine receptor family. Isolates capable of CD4-independent entry have been characterized. We isolated the first CD4-independent HIV-1 isolate, m7NDK, and showed ... |
| 110 | The role of the CD4 receptor versus HIV coreceptors in envelope-mediated apoptosis in peripheral blood mononuclear cells. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:75 (abstract no. 110) Selig SM, Arthos J, Cicala C, White AA, Ravindranath H, Van Ryk D, Steenbeke TD, Machado E, Hanback M, Hanback D, Rabin R, Fauci AS; NIAID, NIH, Bethesda, MD. The depletion of CD4+ T cells, resulting from direct infection and enhanced rates of apoptosis, is a central pathogenic feature of HIV-1 infection. Numerous studies have demonstrated that the viral envelope protein gp120/41 enhances the rate of apoptosis in activated CD4+ T-cells. The HIV-1 viral envelope ... |
| 111 | Mutational analysis of DC-SIGN: a novel HIV envelope binding C-type lectin expressed on dentritic cells. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:75 (abstract no. 111) Pohlmann S, Baribaud F, Leslie G, Lee B, Munch J, Kirchhoff F, Doms RW; Univ of Pennsylvania, Philadelphia. Dendritic cells (DCs) play an important role in primary HIV infection. While HIV replicates poorly in DC cultures, DCs can efficiently transmit virus to co-cultured T-cells. The functional mechanism underlying this phenomenon is not fully understood. Recently DC-SIGN, a novel C-type lectin specific for DCs ... |
| 112 | Production, functional characterization and mapping of monoclonal antibodies to DC-SIGN. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:75 (abstract no. 112) Baribaud F, Pohlmann S, Lee B, Haggarty BS, Sharron M, Hoxie JA, Doms RW; Univ of Pennsylvania, Philadelphia. DC-SIGN, a dendritic cell (DC)-specific C-type lectin highly expressed on DC present in mucosal tissues, has recently been shown to bind ICAM2 and ICAM3 and to efficiently capture human immunodeficiency virus (HIV). Virus captured by DC-SIGN can be efficiently presented to T-cells, resulting in virus ... |
| 113 | DC-SIGNR, a DC-SIGN homologue, binds to HIV and activates infection in trans. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:76 (abstract no. 113) Pohlmann S, Baribaud F, Leslie G, Lee B, Munch J, Kirchhoff F, Doms RW; Univ of Pennsylvania, Philadelphia. DC-SIGN is a novel C-type lectin expressed on the surface of dendritic cells (DCs). Interesting biological properties were ascribed to DC-SIGN: DC-SIGN binds to ICAM-3 and thus contributes to the close interaction between DCs and T-cells that is required for efficient presentation of antigen. DC-SIGN also ... |
| 114 | CD147 is a signaling receptor for extracellular cyclophilin A: role in HIV infection. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:76 (abstract no. 114) Yurchenko V, Zybarth G, Hao T, O'Connor M, Pushkarsky T, Dai WW, Sherry B, Bukrinsky M; Picower Inst for Med Res, Manhasset, NY. Cyclophilin A (CypA) is a ubiquitously distributed intracellular protein belonging to the immunophilin family. CypA possesses peptidyl-prolyl cis-trans isomerase activity and plays an important role in protein folding. In addition, CypA is secreted by cells in response to inflammatory stimuli and is a ... |
| 115 | Structure-function analysis of the anti-HIV activity of sulphated dextrins against R5, X4 and R5X4 viruses. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:76 (abstract no. 115) Shaunak S, Chandler B, Thornton M, Steele S, Jones M; Imperial Coll Sch of Med, Hammersmith Hosp, London, UK. Dextrin 2-sulphate (D2S) blocks the entry of HIV-1, but not HIV-2 or SIV, into PBMN cells. Initial results from a clinical trial suggested that it reduced the viral load in patients with AIDS. Methods: We have (i) studied the anti-HIV-1 effect of changing the percentage sulphation of this molecule from 7.4% ... |
| 116 | Mechanisms of evolution of HIV-1 V1/V2 env variable regions. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:76 (abstract no. 116) McGrath KM, Swanstrom R; Univ of North Carolina at Chapel Hill. The 5 variable regions of the HIV-1 env gene represent the regions of the viral genome with the greatest sequence diversity. The selective forces driving the evolution of these variable regions likely represent important features of virus-host interactions. We have used a heteroduplex tracking assay (HTA) ... |
| 117 | HIV-1 envelope transmembrane subunit (gp41) is required for envelope-induced apoptosis in single uninfected CD4+ T cells. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:77 (abstract no. 117) Blanco J, Barretina J, Gutierrez A, Cabrera C, Clotet B, Este JA; Fundacio irsiCaixa, Barcelona, Spain. Contact between HIV-1 envelope-expressing cells and target CD4+ cells induces cell- to-cell fusion and apoptotic death in fused and in mononuclear CD4+ single cells. Methods: To evaluate the relationships between cell-to-cell fusion and single-cell apoptosis, we have quantified cell-to-cell fusion, total ... |
| 118 | New insights into the functionality of a virion-bound host cell membrane protein: CD28 versus HIV- 1. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:77 (abstract no. 118) Giguere JF, Paquette JS, Bounou S, Tremblay MJ; Infectious Diseases Res Ctr, Ste-Foy, Quebec, Canada. During the budding process, retroviruses acquire several host membrane proteins in their envelope. The presence of such host components in the envelope of HIV-1 has been shown to affect the life cycle of the virus. CD28 is an important costimulatory molecule continuously expressed on T CD4+ lymphocytes. |
| 119 | SHIV clones with mutations in the intracytoplasmic domain of the env gene. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:77 (abstract no. 119) Li J, Shacklett BL, Luciw PA; Univ of California, Davis. The function of the intracytoplasmic domain (ICD) of the HIV/SIV Env glycoprotein is not well understood. This domain contains two amphipathic alpha-helices, also designated lentivirus lytic peptides (LLP), which cause cell lysis and bind to the cellular protein calmodulin. Methods and Results: To study ... |
| 120 | Evidence for a signal reducing the cell surface expression of HIV-1 primary isolate envelope proteins. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:77 (abstract no. 120) Lebigot S, Roingeard P, Barin F, Brand D; Univ of Tours, France. Among the different vaccination strategies elaborated to induce a humoral immunity to prevent HIV-1 infection, envelope glycoproteins derived from T-cell laboratory-adapted (TCLA) viruses have often been chosen as immunogens. However, these envelope glycoproteins have never permitted to induce broad- ... |
| 120B | Biochemical and functional characterization of oligomeric envelope glycoprotein from a primary HIV-1 isolate. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:78 (abstract no. 120B) Staropoli I, Chanel C, Girard M, Altmeyer R; Institut Pasteur, Paris, France. Fusion of HIV-1 with CD4+ T cells is thought to be initiated by a trimeric complex of the envelope glycoprotein gp120/gp41. The structure of gp120/gp41 is maintained by 10 intramolecular disulfide bonds. Non-covalently associated gp120 and gp41 subunits are thought to trimerize via the ectodomain of gp41. Interaction ... |
| 121 | Regulation of cyclin T1 expression. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:78 (abstract no. 121) Martin-Serrano J, Li K, Bieniasz PD; Aaron Diamond AIDS Res Ctr, New York, NY. Cyclin T1 (CycT1) is a subunit of the positive transcription elongation factor-β (P- TEFβ), which is recruited to the TAR RNA element of the HIV promoter by the viral protein Tat to activate viral gene expression. CycT1 is dramatically upregulated upon T-cell activation, suggesting that limited Tat ... |
| 122 | Incorporation of aminoacyl-tRNA(Lys) synthetase into HIV-1. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:78 (abstract no. 122) Cen S, Khorchid A, Javanbakht H, Shiba K, Musier-Forsyth K, Kleiman L; Lady Davis Inst for Med Res, Montreal, Quebec, Canada. tRNA(Lys)3 is the primer for reverse transcription in human immunodeficiency virus. During viral assembly, the tRNA(Lys)3 is selected for incorporation into virions. In the cell tRNA is found in complexes with proteins, such as aminoacyl-tRNA synthetase and eEF1alpha, associated with translation. |
| 123 | Elements of the tRNA acceptor stem and TpsiC stem-loop required for HIV-1 infectivity. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:79 (abstract no. 123) Yu Q, Morrow CD; Univ of Alabama at Birmingham. Background and Methods: In a previous study, we reported the use of an in vivo complementation system to identify elements of a tRNA required for primer selection and use in HIV-1 replication. In this system, a mutant HIV-1 with a primer binding site (PBS) complementary to yeast tRNA(Phe) (psHIV-Phe) relies on exogenou |
| 124 | Analysis of secondary structures within the 5 region of the HIV-1 genome involved in dimerization of viral RNA. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:79 (abstract no. 124) Russell RS, Wainberg MA, Liang C; McGill AIDS Ctr, Lady Davis Inst, Jewish Gen Hosp, Montreal, Quebec, Canada. The HIV-1 RNA genome contains a stem-loop structure (SL1) that is known as the dimerization initiation site (DIS). Mutations in this region resulted in severely diminished replication, but prolonged culture of these DIS mutants resulted in the evolution of viral revertants with replication capacities simila |
| 125 | An intact U5-leader stem of simian immunodeficiency virus is important for viral genomic RNA packaging. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:79 (abstract no. 125) Guan Y, Whitney J, Wainberg MA; McGill AIDS Ctr, Montreal, Quebec, Canada. Both SIV and HIV-1 leader sequences exhibit similar secondary structures, such as TAR, R-U5 stem-loop, U5-leader stem, etc. An intact TAR or R-U5 stem-loop structure was shown to be important for viral RNA packaging in HIV-1. However, the role of the U5-leader stem in either HIV-1 or SIV has not been extens |
| 126 | Inhibition of human immunodeficiency virus type-1 reverse transcription using mutated tRNA(Lys)3 molecules that interfere with formation of the natural initiation complex. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:80 (abstract no. 126) Wei X, Cherry E, Budai B, Sturzl M, Wainberg MA, Gotte M; McGill Univ AIDS Ctr, Lady Davis Inst-Jewish Gen Hosp, Montreal, Quebec, Canada. Reverse transcription of human immunodeficiency virus type-1 (HIV-1) genomic RNA is primed by tRNA(Lys)3, which binds with its 18 terminal nucleotides to the viral primer binding site (PBS). Since the initiation of DNA synthesis was shown to be a highly specific process, it represents a potential target for |
| 127 | Enhancing infectious titers of HIV-1-derived vectors upon non-dividing cells by modulation of the efficiency of reverse transcription. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:80 (abstract no. 127) Dornadula G, Zhang H, Pomerantz RJ; Jefferson Med Coll, Thomas Jefferson Univ, Philadelphia, PA. One of the advantages of utilizing lentivirus-derived vectors for genetic therapy is their ability to infect nondividing cells. However, reverse transcription is a rate-limiting step for the completion of the lentiviral life cycle, especially when quiescent cells are chosen as targets. Methods: In these stu |
| 128 | Near-simultaneous PHA activation and HIV-1 infection of primary CD4+ T-cells generates genetically damaged, hypermutated proviruses. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:80 (abstract no. 128) Janini M, Rogers M, Louder M, Perfetto S, Birx DL, McCutchan F; Henry M. Jackson Fndn, Rockville, MD. Hypermutation, defined as a high rate of G to A substitution in the context GA or GG, has been sporadically observed in HIV-1 sequences from patient PBMC and virus cultures. Patients have not been systematically evaluated for hypermutation, and the cell substrates in which hypermutation occurs have not been |
| 129 | Complete mutational analysis of the HIV protease dimer interface. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:80 (abstract no. 129) Everitt L, Chowdury S, Pettit S, Kaplan AH; Univ of North Carolina at Chapel Hill. The protease of HIV is functional only as a dimer. If dimerization is blocked, either by mutation or by molecules that fit within the dimer interface, enzyme activity is inhibited and noninfectious particles are produced. Structural data indicate that the two protease monomers are joined by a four-stranded |
| 130 | The CD45RO isoform promotes HIV-1 replication through the LTR enhancer region: a key role by the NFAT factor. Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:81 (abstract no |