HIV envelope proteins differentially utilize CXCR4 and CCR5 coreceptors for induction of apoptosis.

The involvement of CXCR4 and CCR5 coreceptors in apoptosis induced by the HIV envelope (Env) proteins has not been well defined. We found that simian human immunodeficiency virus (SHIV) virus-like particles (VLPs) containing HIV Env proteins preferentially induce apoptosis of cells corresponding to their coreceptor usage in a CD4+ T cell line. We also demonstrated that induction of apoptosis by SHIV VLPs is correlated with coreceptor usage in a non-T cell line. We examined the effects of SHIV VLPs containing Env proteins derived from either a T-cell-tropic HIV (BH10) strain or a dual-tropic HIV (89.6) strain on induction of apoptosis in recombinant CD4+ human osteosarcoma (HOS) cells expressing either CXCR4 (HOS-CD4.CXCR4) or CCR5 coreceptors (HOS-CD4.CCR5). HOS-CD4.CXCR4 or HOS-CD4.CCR5 cells were activated with concanavalin A and cocultured with VLPs. By TUNEL (TdT-mediated dUTP-X nick end labeling) fluorescence staining and flow cytometry assays, SHIV BH10 VLPs were found to preferentially induce apoptosis in HOS-CD4.CXCR4 cells but not in HOS-CD4 or HOS-CD4.CCR5 cells. On the other hand, SHIV 89.6 VLPs induced an elevated level of apoptosis in both HOS-CD4.CXCR4 and HOS-CD4.CCR5 cells in a dose-dependent fashion. These data demonstrate that T-cell-tropic BH10 Env preferentially utilizes CXCR4, but not CCR5, for induction of apoptosis, whereas dual-tropic 89.6 Env induces apoptosis in both CXCR4- and CCR5-containing cell lines.

Yao Q ，Compans RW ，Chen C 《VIROLOGY》

The role of the CD4 receptor versus HIV coreceptors in envelope-mediated apoptosis in peripheral blood mononuclear cells.

Arthos J ，Cicala C ，Selig SM ，White AA ，Ravindranath HM ，Van Ryk D ，Steenbeke TD ，Machado E ，Khazanie P ，Hanback MS ，Hanback DB ，Rabin RL ，Fauci AS ... -  《VIROLOGY》

Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor.

Weissman D ，Rabin RL ，Arthos J ，Rubbert A ，Dybul M ，Swofford R ，Venkatesan S ，Farber JM ，Fauci AS ... -  《NATURE》

Primary SIVsm isolates use the CCR5 coreceptor from sooty mangabeys naturally infected in west Africa: a comparison of coreceptor usage of primary SIVsm, HIV-2, and SIVmac.

Chen Z ，Gettie A ，Ho DD ，Marx PA ... -  《VIROLOGY》

CXCR4 and CCR5 on human thymocytes: biological function and role in HIV-1 infection.

Zaitseva MB ，Lee S ，Rabin RL ，Tiffany HL ，Farber JM ，Peden KW ，Murphy PM ，Golding H ... -  《JOURNAL OF IMMUNOLOGY》