Journal
VIROLOGY
Volume 292, Issue 1, Pages 98-106Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/viro.2001.1266
Keywords
CCR5; CXCR4; retrovirus; gp120; TUNEL; annexin-V; T cell
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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. (C) 2002 Elsevier Science.
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