CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells

Nichole R. Klatt, Emi Shudo, Alex M. Ortiz, Jessica C. Engram, Mirko Paiardini, Benton Lawson, Michael D. Miller, James Else, Ivona Pandrea, Jacob D. Estes, Cristian Apetrei, Joern E. Schmitz, Ruy M. Ribeiro, Alan S. Perelson, Guido Silvestri

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

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 SIVinfected 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.

Original languageEnglish (US)
Article numbere1000747
JournalPLoS pathogens
Volume6
Issue number1
DOIs
StatePublished - Jan 2010

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Klatt, N. R., Shudo, E., Ortiz, A. M., Engram, J. C., Paiardini, M., Lawson, B., Miller, M. D., Else, J., Pandrea, I., Estes, J. D., Apetrei, C., Schmitz, J. E., Ribeiro, R. M., Perelson, A. S., & Silvestri, G. (2010). CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells. PLoS pathogens, 6(1), [e1000747]. https://doi.org/10.1371/journal.ppat.1000747