title: The role of the CD4 receptor versus HIV coreceptors in envelope-mediated apoptosis in peripheral blood mononuclear cells.
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.
authors.affiliation: Laboratory of Immunoregulation, National Institutes of Health, Bethesda, Maryland 20892, USA. JArthos@nih.gov
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Claudia
authors.initials: C
authors.lastname: Cicala
authors.forename: Sara M
authors.initials: SM
authors.lastname: Selig
authors.forename: Andrew A
authors.initials: AA
authors.lastname: White
authors.forename: Hanumanth M
authors.initials: HM
authors.lastname: Ravindranath
authors.forename: Donald
authors.initials: D
authors.lastname: Van Ryk
authors.forename: Tavis D
authors.initials: TD
authors.lastname: Steenbeke
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Machado
authors.forename: Prateeti
authors.initials: P
authors.lastname: Khazanie
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Hanback
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Hanback
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Rabin
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: 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
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV