Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque

J Clin Invest. 2011 Jun;121(6):2391-400. doi: 10.1172/JCI45235. Epub 2011 May 9.


High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4⁺ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4⁺ and CD8⁺ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4⁺ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cercocebus atys / genetics*
  • Cercocebus atys / metabolism
  • Disease Progression
  • Disease Susceptibility
  • Gene Expression Profiling*
  • Gene Expression Regulation, Viral*
  • HIV Infections / genetics*
  • HIV Infections / metabolism
  • HIV Long-Term Survivors*
  • HIV-1* / physiology
  • Humans
  • Macaca mulatta / genetics*
  • Macaca mulatta / metabolism
  • Phenotype
  • Simian Acquired Immunodeficiency Syndrome / genetics*
  • Simian Acquired Immunodeficiency Syndrome / metabolism
  • Simian Immunodeficiency Virus* / physiology
  • Species Specificity
  • Up-Regulation
  • Viral Load
  • Viremia / genetics
  • Viremia / metabolism
  • Virus Replication

Associated data

  • GEO/GSE28128