Depletion of CD4⁺ T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques

Alexandra M Ortiz, Nichole R Klatt, Bing Li, Yanjie Yi, Brian Tabb, Xing Pei Hao, Lawrence Sternberg, Benton Lawson, Paul M Carnathan, Elizabeth M Cramer, Jessica C Engram, Dawn M Little, Elena Ryzhova, Francisco Gonzalez-Scarano, Mirko Paiardini, Aftab A Ansari, Sarah Ratcliffe, James G Else, Jason M Brenchley, Ronald G CollmanJacob D Estes, Cynthia A Derdeyn, Guido Silvestri

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

CD4+ T cells play a central role in the immunopathogenesis of HIV/AIDS, and their depletion during chronic HIV infection is a hallmark of disease progression. However, the relative contribution of CD4+ T cells as mediators of antiviral immune responses and targets for virus replication is still unclear. Here, we have generated data in SIV-infected rhesus macaques (RMs) that suggest that CD4+ T cells are essential in establishing control of virus replication during acute infection. To directly assess the role of CD4+ T cells during primary SIV infection, we in vivo depleted these cells from RMs prior to infecting the primates with a pathogenic strain of SIV. Compared with undepleted animals, CD4+ lymphocyte-depleted RMs showed a similar peak of viremia, but did not manifest any post-peak decline of virus replication despite CD8+ T cell- and B cell-mediated SIV-specific immune responses comparable to those observed in control animals. Interestingly, depleted animals displayed rapid disease progression, which was associated with increased virus replication in non-T cells as well as the emergence of CD4-independent SIV-envelopes. Our results suggest that the antiviral CD4+ T cell response may play an important role in limiting SIV replication, which has implications for the design of HIV vaccines.

Original languageEnglish (US)
Pages (from-to)4433-45
Number of pages13
JournalThe Journal of clinical investigation
Volume121
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • Animals
  • Antilymphocyte Serum/administration & dosage
  • Base Sequence
  • CD4 Antigens/immunology
  • CD4-Positive T-Lymphocytes/immunology
  • DNA Primers/genetics
  • Lymphocyte Depletion
  • Macaca mulatta
  • RNA, Viral/genetics
  • Simian Acquired Immunodeficiency Syndrome/immunology
  • Simian Immunodeficiency Virus/genetics
  • Viral Load/immunology
  • Viremia/immunology
  • Virus Replication/immunology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

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