CD8+ Lymphocytes Control Viral Replication in SIVmac239-Infected Rhesus Macaques without Decreasing the Lifespan of Productively Infected Cells

PLoS Pathogens

Cristian Apetrei¹  Ruy M. Ribeiro²  Jessica C. Engram³  Mirko Paiardini³  Nichole R. Klatt³  Benton Lawson³  James Else⁴  Alan S. Perelson⁵  Alex M. Ortiz⁵  Guido Silvestri⁵  Jacob D. Estes⁶  Joern E. Schmitz⁶  Michael D. Miller⁷  Emi Shudo⁷  Ivona Pandrea⁷ 

[1] AIDS and Cancer Virus Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, Maryland, United States of America;Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America;Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;Gilead Sciences, Inc., Foster City, California, United States of America;Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America;Tulane National Primate Research Center and Tulane Health Sciences Center, Tulane University, New Orleans, Louisiana, United States of America;Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America

关键词: Cytotoxic T cells;    T cells;    Lymphocytes;    SIV;    Viral replication;    Antiretroviral therapy;    Viral load;    Viremia;   

DOI  :  10.1371/journal.ppat.1000747

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication.

【 授权许可】

CC BY