Transcription profiling of CD4⁺ T cells in rhesus macaques that infected with simian-human immunodeficiency virus and re-challenged with SIVmac251

J Med Primatol. 2015 Oct;44(5):263-74. doi: 10.1111/jmp.12185. Epub 2015 Aug 31.

Abstract

Background: Insights into the host factors that contribute to an effective antiviral immune response may be obtained by examining global gene expression in simian-human immunodeficiency virus (SHIV)-infected non-human primates that exhibit different virological outcomes.

Methods: Six chronically SHIV-infected macaques were rectally challenged with SIVmac251. Viral RNA and proviral DNA load in blood were measured. Gene expression profiles in CD4+ T cells were examined and compared between animals with different levels of infection following challenge.

Results and conclusions: Viral RNA was markedly controlled in four challenged animals, whereas two animals had persistent high viremia. Analysis of the gene expression profiles at early infection revealed gene expression signatures between protectors and non-protectors and identified potential protective biomarkers. Pathway analyses revealed that IFN pathway genes are down-regulated in protectors compared to unprotectors. This study suggests that high levels of expression of type 1 IFN-related genes may paradoxically promote virus replication.

Keywords: HIV; gene expression; immune activation; microarray; protective marker; simian-immunodeficiency virus; vaccine.

MeSH terms

  • Animals
  • Antibodies, Viral / blood*
  • CD4 Lymphocyte Count
  • Gene Expression Profiling
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Macaca mulatta
  • Male
  • Simian Acquired Immunodeficiency Syndrome / genetics*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / immunology*
  • Simian Immunodeficiency Virus / isolation & purification
  • Simian Immunodeficiency Virus / physiology
  • Viremia

Substances

  • Antibodies, Viral