Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo.
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.
Fitzgerald
Wendy
W
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.
Sylwester
Andrew W
AW
Grivel
Jean-Charles
JC
Lifson
Jeffrey D
JD
Margolis
Leonid B
LB
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*
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