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14th International AIDS ConferenceBarcelona, Spain — July 7-12, 2002 |
Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. MoOrA1004
BACKGROUND: Macrophages are important target cells for HIV infection and contribute to pathogenesis by serving as a long-lived viral reservoir. Culture or cytokine activated macrophages are more susceptible to HIV infection, as compared with monocytes. Identification of cellular factors that are involved in efficient HIV macrophage infection (in addition to CD4 and chemokine receptors) may lead to novel antiretroviral therapies.
METHODS: A myeloid cell-specific monoclonal antibody (mAb) library (n=142) was screened for increased binding to 7 day cultured macrophages, as compared with fresh monocytes, and antibodies to upregulated surface molecules were assessed for their ability to inhibit HIV infection. Levels of infection were monitored by quantitative PCR and by p24 ELISA. A luciferase reporter gene was used to measure cell-cell fusion and quantitative FACS (QFACS) analysis was used to measure changes in receptor/coreceptor levels following CD63 transfection.
RESULTS: Pretreatment with anti-CD63 mAb was shown to inhibit infection of primary macrophages by M-tropic (R5) and dual tropic (R5X4) strains of HIV-1, but not CXCR4-utilizing isolates. The block to productive infection occurred post-fusion, as assessed by macrophage cell-cell fusion assays, but prior to reverse transcription, as determined by quantitative PCR assay for new viral DNA formation. CD63 cotransfection was also associated with a 7-fold increase in CD4 antibody binding sites per cell by QFACS analysis, whether or not expression of CCR5 or CXCR4 was induced. CCR5 and CXCR4 levels were not affected by CD63 coexpression or by anti-CD63 treatment.
CONCLUSIONS: It is likely that CD63 is involved in HIV infection of macrophages, particularly at a post-fusion step of virus entry. A potential mechanism of action is the maintenance of CD4 expression by reduction of CD4 turnover in macrophages.
Presenting author: Jana von Lindern
1University of Texas Medical Branch, UTMB Div. of Infectious Disease, 301 University Blvd., Route 0435, Galveston, TX 77555, United States.
2University of California Los Angeles, Los Angeles, CA, United States.
3University of Pennsylvania, Philadelphia, PA, United States.
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MoOrA1004
Copyright © 2002 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.
