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

Virology. 2001 Jun 20;285(1):128-37. doi: 10.1006/viro.2001.0927.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis* / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Line
  • Concanavalin A / pharmacology
  • Gene Products, gag / immunology
  • HIV Envelope Protein gp120 / immunology
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp160 / immunology
  • HIV Envelope Protein gp160 / metabolism
  • HIV Infections / etiology
  • HIV-1*
  • Humans
  • Receptors, CCR5 / immunology
  • Receptors, CCR5 / physiology*
  • Receptors, CXCR4 / immunology
  • Receptors, CXCR4 / physiology*
  • Tumor Cells, Cultured
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism*


  • Gene Products, gag
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp160
  • Receptors, CCR5
  • Receptors, CXCR4
  • Viral Envelope Proteins
  • Concanavalin A