The role of the CD4 receptor versus HIV coreceptors in envelope-mediated apoptosis in peripheral blood mononuclear cells

被引:30
|
作者
Arthos, J [1 ]
Cicala, C [1 ]
Selig, SM [1 ]
White, AA [1 ]
Ravindranath, HM [1 ]
Van Ryk, D [1 ]
Steenbeke, TD [1 ]
Machado, E [1 ]
Khazanie, P [1 ]
Hanback, MS [1 ]
Hanback, DB [1 ]
Rabin, RL [1 ]
Fauci, AS [1 ]
机构
[1] Natl Inst Hlth, NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA
关键词
CCR5; CXCR4; retrovirus; gp120; TUNEL; annexin-V; T cell;
D O I
10.1006/viro.2001.1266
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:98 / 106
页数:9
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