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 infection of immortalized lymphoid cell lines, peripheral blood mononuclear cells (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 infection 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 no activity against infection of either monocyte-derived macrophages or brain microglia. In contrast, 12G5 had little or no effect on infection of CEMx174 cells with HIV-1(IIIB) or HIV-1(HxB). To identify the region 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 loop of HIV-1(HxB) was not inhibited by the antibody. A similar pattern was seen in infections of a U87 glioblastoma line that coexpresses CD4 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 HIV-1(IIIB). Taken together, these results suggest that different strains of HIV-1 may interact with different sites on CXCR-4 or may have different binding affinities for the coreceptor.
Strizki
J M
JM
Department of Neurology and Microbiology, University of Pennsylvania Medical Center, Philadelphia 19104-6146, USA.
Turner
J D
JD
Collman
R G
RG
Hoxie
J
J
González-Scarano
F
F
D000911:Antibodies, Monoclonal / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion; D002460:Cell Line; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000032:analysis; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000302:isolation & purification / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D017628:Microglia / Q000166:cytology / Q000821:virology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D008565:Membrane Proteins; D010446:Peptide Fragments; D019718:Receptors, CXCR4; D015728:Receptors, HIV