CD4-independent utilization of the CXCR4 chemokine receptor by HIV-1 and HIV-2

Citation
Ja. Hoxie et al., CD4-independent utilization of the CXCR4 chemokine receptor by HIV-1 and HIV-2, J REPRO IMM, 41(1-2), 1998, pp. 197-211
Citations number
56
Categorie Soggetti
Immunology
Journal title
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
ISSN journal
01650378 → ACNP
Volume
41
Issue
1-2
Year of publication
1998
Pages
197 - 211
Database
ISI
SICI code
0165-0378(199812)41:1-2<197:CUOTCC>2.0.ZU;2-2
Abstract
HIV entry is mediated by an interaction between CD4 and members of the chem okine receptor family of proteins. It is likely that CD4 induces conformati onal changes in the viral envelope glycoproteins that facilitate a subseque nt interaction with the chemokine receptor. To understand these events, var iants of HIV-2 and HIV-I have been derived that are able to interact direct ly with CXCR4 in the absence of CD4. One HIV-2 variant, termed HIV-2/vcp, h as an expanded host range that includes CXCR4(+)/CD4(-) lymphoid and nonlym phoid cell lines. In contrast to T-tropic isolates of HIV-I, HIV-2/vcp was shown to induce >95% downregulation of CXCR4 on chronically infected cells and was able to superinfect HIV-l-infected cells. A variant of HIV-1/IIIB t ermed HIV-1/IIIBx was also derived that is both replication competent and f usogenic for a CD4-negative subclone of SupT1 cells, termed BC7. Infection of BC7 cells by HIV-1/IIIBx was resistant to anti-CD4 monoclonal antibodies but inhibited by the anti-CXCR4 mAb, 12G5. HIV-1/IIIBx was highly fusogeni c on 3T3 cells expressing CXCR4 in the absence of CD4. In contrast to HIV-2 /vcp, the host range of HIV-1/IIIBx was highly restricted and replication i n several CD4(+)/CXCR4(+) lymphoid cell lines was reduced compared to HIV-1 /IIIB. In addition, HIV-1/IIIBx failed to downregulate CXCR4 on chronically infected cells. These studies indicate that HIV-1 and HIV-2 variants can b e derived in vitro that utilize CXCR4 in the absence of CD4. Although the m echanism(s) for these changes remain unclear, possibilities include an incr eased avidity of the viral envelope glycoprotein for CXCR4 and/or the incre ased exposure of the chemokine receptor binding site. Further biochemical a nd molecular analysis of the envelope glycoproteins from these viruses shou ld be helpful in addressing these and other possibilities. (C) 1998 Elsevie r Science Ireland Ltd. All rights reserved.