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Early Establishment and Antigen Dependence of Simian Immunodeficiency Virus-Specific CD8+ T-Cell Defects
Journal article   Open access   Peer reviewed

Early Establishment and Antigen Dependence of Simian Immunodeficiency Virus-Specific CD8+ T-Cell Defects

Yvonne M. Mueller, Constantinos Petrovas, Duc H. Do, Susan R. Altork, Tracy Fischer-Smith, Jay Rappaport, John D. Altman, Mark G. Lewis and Peter D. Katsikis
Journal of virology, v 81(20), pp 10861-10868
01 Aug 2007
DOI: https://doi.org/10.1128/JVI.00813-07
PMID: 17670818
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1128/jvi.00813-07View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Cellular Response to Infection
Differentiation and survival defects of human immunodeficiency virus (HIV)-specific CD8 + T cells may contribute to the failure of HIV-specific CD8 + T cells to control HIV replication. It is not known, however, whether simian immunodeficiency virus (SIV)-infected rhesus macaques show comparable defects in these virus-specific CD8 + T cells or when such defects are established during infection. Peripheral blood cells from acutely and chronically infected rhesus macaques were stained ex vivo for memory subpopulations and examined by in vitro assays for apoptosis sensitivity. We show here that SIV-specific CD8 + T cells from chronically SIV infected rhesus macaques show defects comparable to those observed in HIV infection, namely, a skewed CD45RA − CD62L − effector memory phenotype, reduced Bcl-2 levels, and increased levels of spontaneous and CD95-induced apoptosis of SIV-specific CD8 + T cells. Longitudinal studies showed that the survival defects and phenotype are established early in the first few weeks of SIV infection. Most importantly, they appear to be antigen driven, since most probably the loss of epitope recognition due to viral escape results in the reversal of the phenotype and reduced apoptosis sensitivity, something we observed also for animals treated with antiretroviral therapy. These findings further support the use of SIV-infected rhesus macaques to investigate the phenotypic changes and apoptotic defects of HIV-specific CD8 + T cells and indicate that such defects of HIV-specific CD8 + T cells are the result of chronic antigen stimulation.

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Web of Science research areas
Virology
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