4th Conference on Retroviruses and Opportunistic Infections Washington, DC - January 22-26, 1997

Conf Retroviruses Opportunistic Infect 1997 Jan 22-26; 4th:68 (abstract no. 17)

Strizki JM, Turner J, Collman R, Hoxie J, Gonzalez-Scarano F; University of Pennsylvania, Philadelphia, PA.

CXCR-4, a member of the C-X-C chemokine receptor family, has been shown to function as a co-factor for fusion and infection of T cell tropic HIV-1 isolates. We used a monoclonal antibody directed against an extracellular domain of CXCR-4 to investigate the role of this receptor in infection of immortalized T-cells, T/B cell hybrids and PBMCs by different HIV-1 strains. Addition of the 12G5 antibody to cells prior to and during infection with the dual tropic virus HIV(89.6), inhibited p24 production by 2-4 logs in CEMx174 cells, 174-CD4 cells and PBMCs. In contrast, 12G5 failed to inhibit infection of HIV(89.6) in either monocyte derived macrophages (MDM) or in brain microglia. Interestingly, 12G5 had little or no effect on infection of HIV(HxB) in CEMx174 cells, and showed only a limited and inconsistent ability to inhibit infection in PBMCs. To identify possible regions of the viral envelope involved in the interaction with CXCR-4 we utilized chimeric molecularly cloned viruses which have interchanged the V3 loop and CD4 binding regions of gp120 between the HIV(HxB) and HIV(89.6) viruses. Chimerics containing the V3 loop region of HIV(89.6) were inhibited by 12G5 to the same degree as wild type HIV(89.6), whereas those viruses containing the V3 loop of HIV(HxB) were not significantly inhibited. Taken together these results suggest that HIV(89.6) may utilize an epitope on CXCR4 that can be blocked by the 12G5 antibody and is distinct from the epitope used by HIV(HxB), and that the V3 loop region is important in the interaction between HIV-1 and CXCR4.

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