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  • Title: The role of the CD4 receptor versus HIV coreceptors in envelope-mediated apoptosis in peripheral blood mononuclear cells.
    Author: 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.
    Journal: Virology; 2002 Jan 05; 292(1):98-106. PubMed ID: 11878912.
    Abstract:
    We examined the role of CD4, CXCR4, and CCR5 in HIV envelope-mediated apoptosis by measuring the response of activated PBMCs to recombinant envelope proteins derived from CXCR4- and CCR5-utilizing viruses. Apoptosis of T cells was assessed by annexin-V staining and TdT-mediated dUTP-biotin nick-end labeling. Treatment of CCR5Delta32 homozygote PBMCs with a CCR5-specific envelope induced apoptosis in T cells, demonstrating that envelope--CD4 interactions are sufficient to induce apoptosis. However, a CXCR4-specific envelope induced higher levels of apoptosis than a CCR5-specific envelope, suggesting that envelope-mediated apoptosis can be enhanced by envelope--CXCR4 interactions. We conclude that envelope can induce apoptosis in T cells independently of the coreceptor specificity of a given envelope, or the expression profile of CXCR4 or CCR5 on a target cell. However, envelope--coreceptor interactions, and in particular, envelope--CXCR4 interactions, can contribute to this process.
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