The Role of the CD4 Receptor versus HIV Coreceptors in Envelope-Mediated Apoptosis in Peripheral Blood Mononuclear Cells

AbstractWe 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 CCR5Δ32 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