AEGiS-15IAC: Selective LD78[beta production by PBMCs during HTLV-2 infection induce resistance to HIV-1 entry.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Selective LD78[beta production by PBMCs during HTLV-2 infection induce resistance to HIV-1 entry.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. TuOrA1186)

Casoli C, Pilotti E, Elviri L, Campanini B, Mozzarelli A, Careri M, Vicenzi E, Bertazzoni U, Re MC, Berghenti F, Caccavari R, Poli G
University of Parma, Parma, Italy

BACKGROUND: A substantial percentage (10-20%) of IDUs in the world are co-infected with HIV-1 and HTLV-2. We have demonstrated that in co-infected subjects, induction of CCL3/MIP-1ialpha and other T-cell factor(s) by HTLV-2 may lead to inhibition of HIV infection. This study is aiming at understanding the influence of HTLV-2 on the expression of the two isoforms of MIP-1ialpha in PBMC cultures from HTLV-2 infected/HIV-1 exposed seronegative (HTLV-2/HIV-1 ESN) individuals. LTNP HIV-1/HTLV-2 co-infected and LTNP HIV-1 mono-infected subjects were included in this study.

METHODS: The isoforms CCL3/LD78ialpha and CCL3L1/LD78[beta of MIP-1ialpha were purified from PBMC cultures by a multi-step isolation procedure and identified by Mass Spectrometry. Antigen HIV-1 driven MIP-1ialpha production was evaluated by immunoassays. Viral production was evaluated in cultures of unstimulated HTLV-2-mono-infected PBMCs that had been infected with R5 HIV-1 strains, in the presence or in the absence of neutralizing antibodies against CC-chemokines.

RESULTS: The analyses evidenced a co-existence of LD78ialpha and LD78[beta in PBMC-derived supernatants from HTLV-2/HIV-1 ESN and LTNP HIV-1/HTLV-2 subjects and revealed that the [beta form was preferentially expressed (1.6 fold). Physiologically, LD78ialpha/[beta act as aggregates and have potent activity in inducing down regulation (50%) of CCR5 receptor on monocyte/macrophage subsets. Stimulation of HTLV-2/HIV-1 ESN PBMCs with gp120-C5 peptide induced an increase of 3-5 fold of MIP-1 with respect to unstimulated controls. The decreased efficiency of R5 HIV-1 replication in PBMC from HTLV-2/HIV-1 ESN (2.5 log less than in controls) was due to the presence of MIP-1ialpha, as assessed with neutralizing antibodies to each CC-chemokine. Conclusion These results support the hypothesis that HTLV-2 may curtail HIV-1 infection and delay AIDS progression in co-infected patients by upregulating the most potent HIV-1-inhibitory chemokine CCL3L1/LD78[beta. The University of Parma partecipates in the City-AIDS program/UNAIDS.

Keywords: AEGIS, HIV-1, Macrophage Inflammatory Protein-1, HIV Infections, Deltaretrovirus Infections, Human T-lymphotropic virus 2, Receptors, CCR5, Acquired Immunodeficiency Syndrome, Virus Replication, HTLV-II Infections, Chemokines, CC, HIV Envelope Protein gp120, Monocytes, Chemokines, T-Lymphocytes, Humans, virology, immunology

040711
TuOrA1186