The efficacy of T cell-mediated immune responses is reduced by the envelope protein of the chimeric HIV-1/SIV-KB9 virus in vivo.
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 TGFbeta, 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.
Stevceva
Liljana
L
Partners AIDS Research Center and Infectious Diseases Medicine, Massachusetts General Hospital (East), Charlestown, MA 02129, USA. lstevceva@hotmail.com
Yoon
Victor
V
Carville
Angela
A
Pacheco
Beatriz
B
Santosuosso
Michael
M
Korioth-Schmitz
Birgit
B
Mansfield
Keith
K
Poznansky
Mark C
MC
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007111:Immunity, Cellular; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology; D016212:Transforming Growth Factor beta / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; D014759:Viral Envelope Proteins; C514793:gp120 protein, Human immunodeficiency virus 1; C069623:gp120 protein, Simian immunodeficiency virus