title: HIV envelope proteins differentially utilize CXCR4 and CCR5 coreceptors for induction of apoptosis.
abstract: 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.
authors: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. qyao@bimcore.emory.edu
authors: Q
authors: Q
authors: Yao
authors: R W
authors: RW
authors: Compans
authors: C
authors: C
authors: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D015683:Gene Products, gag / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000209:etiology; D015497:HIV-1; D006801:Humans; D019713:Receptors, CCR5 / Q000276:immunology / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D015683:Gene Products, gag; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014759:Viral Envelope Proteins; D003208:Concanavalin A