A monoclonal antibody (12G5) directed against CXCR-4 inhibits infection with the dual-tropic human immunodeficiency virus type 1 isolate HIV- 189.6 but not the T-tropic isolate HIV-1(HxB)

J. M. Strizki, J. D. Turner, R. G. Collman, J. Hoxie, F. Gonzalez-Scarano

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

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-189.6) and a T-tropic strain (HIV-1(IIIB)). Addition of antibody 12G5 to cells prior to and during infection with HIV- 189.6 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-189.6 envelope that confers sensitivity to 12G5, we used chimeric molecular clones. Chimeras containing the V3 loop region of HIV-189.6 were inhibited by 12G5 to the same degree as wild-type HIV-189.6 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- 189.6 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.

Original languageEnglish (US)
Pages (from-to)5678-5683
Number of pages6
JournalJournal of virology
Volume71
Issue number7
DOIs
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint

Dive into the research topics of 'A monoclonal antibody (12G5) directed against CXCR-4 inhibits infection with the dual-tropic human immunodeficiency virus type 1 isolate HIV- 1<sub>89.6</sub> but not the T-tropic isolate HIV-1(HxB)'. Together they form a unique fingerprint.

Cite this