A MONOCLONAL-ANTIBODY (12G5) DIRECTED AGAINST CXCR-4 INHIBITS INFECTION WITH THE DUAL-TROPIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATE HIV-1(89.6) BUT NOT THE T-TROPIC ISOLATE HIV-1(HXB)

We used a monoclonal antibody (12G5) directed against an extracellular domain of CXCR-4 to investigate the role of this receptor in infectio n of immortalized lymphoid cell lines, peripheral blood mononuclear ce lls (PBMCs), and primary brain microglia with a dual-tropic strain of human immunodeficiency virus (HIV-1(89.6)) and a T-tropic strain (HIV- 1(IIIB)). Addition of antibody 12G5 to cells prior to and during infec tion with HIV-1(89.6) inhibited p24 production 100- to 10,000-fold in CEMx174 and 174-CD4 cells and about 10-fold in PBMC cultures but had n o activity against infection of either monocyte-derived macrophages or brain microglia, In contrast, 12G5 had little or no effect on infecti on of CEMx174 cells with HIV-1(IIIB) or HIV-1(HxB). To identify the re gion of the HIV-1(89.6) envelope that confers sensitivity to 12G5, we used chimeric molecular clones, Chimeras containing the V3 loop region of HIV-1(89.6) were inhibited by 12G5 to the same degree as wild-type HIV-1(89.6), whereas replication of those viruses containing the V3 L oop of HIV-1(HxB) was not inhibited by the antibody, A similar pattern was seen in infections of a U87 glioblastoma line that coexpresses CD 4 and CXCR-4. Antibody 12G5 was also able to block fusion between HeLa -CD4 cells and CEMx174 cells chronically infected with HIV-1(89.6) but had no effect on fusion mediated by cells chronically infected with H IV-1(IIIB). Taken together, these results suggest that different strai ns of HIV-1 may interact with different sires on CXCR-4 or may have di fferent binding affinities for the coreceptor.