Rate of AIDS progression is associated with gastrointestinal dysfunction in simian immunodeficiency virus-infected pigtail macaques

Lauren A Canary, Carol L Vinton, David R Morcock, Jordan B Pierce, Jacob D Estes, Jason M Brenchley, Nichole R Klatt

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

During HIV/SIV infection, mucosal immune system dysfunction and systemic immune activation are associated with progression to AIDS; however, it is unclear to what extent pre-existing gastrointestinal damage relates to disease progression postinfection. Pigtail macaques (PTM) are an excellent model in which to assess mucosal dysfunction in relation to HIV/SIV pathogenesis, as the majority of these animals have high levels of gastrointestinal damage, immune activation, and microbial translocation prior to infection, and rapidly progress to AIDS upon SIV infection. In this study, we characterized the mucosal immune environment prior to and throughout SIV infection in 13 uninfected PTM and 9 SIV-infected PTM, of which 3 were slow progressors. This small subset of slow progressors had limited innate immune activation in mucosal tissues in the periphery, which was associated with a more intact colonic epithelial barrier. Furthermore, we found that preinfection levels of microbial translocation, as measured by LPS-binding protein, in PTM correlated with the rate of progression to AIDS. These data suggest that pre-existing levels of microbial translocation and gastrointestinal tract dysfunction may influence the rate of HIV disease progression.

Original languageEnglish (US)
Pages (from-to)2959-65
Number of pages7
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume190
Issue number6
DOIs
StatePublished - Mar 15 2013

Keywords

  • Acquired Immunodeficiency Syndrome/immunology
  • Animals
  • Disease Models, Animal
  • Disease Progression
  • Gastrointestinal Diseases/immunology
  • Intestinal Mucosa/immunology
  • Macaca nemestrina
  • Simian Acquired Immunodeficiency Syndrome/immunology
  • Simian Immunodeficiency Virus/immunology
  • Time Factors
  • Viral Load/immunology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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