title: Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo.
abstract: Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4(+) T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4(+) T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4(+) T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus.
authors.affiliation: Laboratory of Cellular and Molecular Biophysics and NASA/NIH Center for Three-Dimensional Tissue Culture, National Institutes of child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1855, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Fitzgerald
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Sylwester
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Grivel
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Leonid B
authors.initials: LB
authors.lastname: Margolis
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D004220:Disulfides / Q000494:pharmacology; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D016877:Oxidants / Q000494:pharmacology; D014066:Palatine Tonsil / Q000276:immunology* / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014771:Virion / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D017077:Culture Media, Conditioned; D004220:Disulfides; D015483:HIV Antibodies; D016877:Oxidants; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl