The role of the CD4 receptor versus HIV coreceptors in envelope-mediated apoptosis in peripheral blood mononuclear cells.
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.
Arthos
James
J
Laboratory of Immunoregulation, National Institutes of Health, Bethesda, Maryland 20892, USA. JArthos@nih.gov
Cicala
Claudia
C
Selig
Sara M
SM
White
Andrew A
AA
Ravindranath
Hanumanth M
HM
Van Ryk
Donald
D
Steenbeke
Tavis D
TD
Machado
Elizabeth
E
Khazanie
Prateeti
P
Hanback
Meredith S
MS
Hanback
Douglas B
DB
Rabin
Ronald L
RL
Fauci
Anthony S
AS
D017209:Apoptosis / Q000187:drug effects; D015704:CD4 Antigens / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000502:physiology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV