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Journal of Virology, July 2004, p. 7061-7068, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.7061-7068.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Noninfectious X4 but Not R5 Human Immunodeficiency Virus Type 1 Virions Inhibit Humoral Immune Responses in Human Lymphoid Tissue Ex Vivo

Wendy Fitzgerald,1 Andrew W. Sylwester,1 Jean-Charles Grivel,1 Jeffrey D. Lifson,2* and Leonid B. Margolis1*

Laboratory of Cellular and Molecular Biophysics and NASA/NIH Center for Three-Dimensional Tissue Culture, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1855,1 AIDS Vaccine Program, SAIC Frederick, Inc., National Cancer Institute—Frederick, Frederick, Maryland 21702-12012

Received 28 October 2003/ Accepted 25 February 2004

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.

* Corresponding author. Mailing address for L. B. Margolis: National Institute of Child Health and Human Development, National Institutes of Health, Building 10, Room 10D14, 10 Center Dr., Bethesda, MD 20892-1855. Phone: (301) 594-2476. Fax: (301) 480-0857. E-mail: margolis{at}helix.nih.gov. Mailing address for J. D. Lifson: AIDS Vaccine Program, SAIC Frederick, Inc., National Cancer Institute—Frederick, Frederick, MD 21702-1201. E-mail: lifson{at}ncifcrf.gov.

Journal of Virology, July 2004, p. 7061-7068, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.7061-7068.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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