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The Efficacy of T Cell-Mediated Immune Responses Is Reduced by the Envelope Protein of the Chimeric HIV-1/SIV-KB9 Virus In Vivo¹

Liljana Stevceva^2,*, Victor Yoon^*, Angela Carville, Beatriz Pacheco, Michael Santosuosso^*, Birgit Korioth-Schmitz, Keith Mansfield and Mark C. Poznansky^2,*

^* Partners AIDS Research Center and Infectious Diseases Medicine, Massachusetts General Hospital (East), Charlestown, MA 02129; New England Primate Research Center, Harvard Medical School, Southborough, MA 01772; Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115; and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215

Gp120 is a critical component of the envelope of HIV-1. Its role in viral entry is well described. In view of its position on the viral envelope, gp120 is a part of the retrovirus that immune cells encounter first and has the potential to influence antiretroviral immune responses. We propose that high levels of gp120 are present in tissues and may contribute to the failure of the immune system to fully control and ultimately clear the virus. Herein, we show for the first time that lymphoid tissues from acutely HIV-1/SIV (SHIV)-KB9-infected macaques contain deposits of gp120 at concentrations that are high enough to induce suppressive effects on T cells, thus negatively regulating the antiviral CTL response and contributing to virus survival and persistence. We also demonstrate that SHIV-KB9 gp120 influences functional T cell responses during SHIV infection in a manner that suppresses degranulation and cytokine secretion by CTLs. Finally, we show that regulatory T cells accumulate in lymphoid tissues during acute infection and that they respond to gp120 by producing TGFβ, a known suppressant of cytotoxic T cell activity. These findings have significant implications for our understanding of the contribution of non-entry-related functions of HIV-1 gp120 to the pathogenesis of HIV/AIDS.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ M.C.P. and L.S. were supported by Public Health Service Grants RO1 AI49757 and T32A1007387, respectively.

² Address correspondence and reprint requests to Dr. Liljana Stevceva and Dr. Mark C. Poznansky, Partners AIDS Research Center and Infectious Diseases Medicine, Massachusetts General Hospital (East), Building 149, Room 5234, Charlestown, MA 02129. E-mail address: lstevceva{at}hotmail.com and mpoznansky{at}partners.org

³ Abbreviations used in this paper: PB, peripheral blood; LN, lymph node; SIV, simian immunodeficiency virus; SHIV, chimeric HIV-1/SIV virus; Treg, regulatory T cell.

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