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Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo

  1. Author:
    Fitzgerald, W.
    Sylwester, A. W.
    Grivel, J. C.
    Lifson, J. D.
    Margolis, L. B.

  2. Author Address

    Lifson, JD, NICHHD, Lab Cellular & Mol Biophys, NIH, Bldg 10,Room 10D14,10 Ctr Dr, Bethesda, MD 20892 USA NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NICHHD, NASA, Ctr 3 Dimens Tissue Culture, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, AIDS Vaccine Program, Natl Canc Inst, Frederick, MD 21702 USA.
    1. Year: 2004
  2. Journal: Journal of Virology
    1. 78
    2. 13
    3. Pages: 7061-7068
  4. Type of Article: Article
  1. 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

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