Human TRIM5alpha expression levels and reduced susceptibility to HIV-1 infection

J Infect Dis. 2009 Jun 1;199(11):1657-63. doi: 10.1086/598861.

Abstract

Background: Human TRIM5alpha (TRIM5alphahu), a member of the tripartite motif protein family, displays some anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro, although it is substantially less potent than its rhesus monkey counterpart (TRIM5alpharh). The effects of levels of TRIM5alphahu on prevention or control of HIV-1 infection in vivo are unknown.

Methods: We used a quantitative real-time polymerase chain reaction (PCR) assay to measure levels of TRIM5alphahu expression in peripheral blood mononuclear cells (PBMCs) obtained from a cohort of individuals at high risk for HIV-1 infection in Durban, South Africa. Samples were available from 38 infected subjects (with all these samples obtained within 1 year of infection) and from 57 uninfected persons. Matched preinfection and postinfection samples were available from 13 individuals.

Results: TRIM5alphahu messenger RNA levels were lower in the PBMCs of HIV-1-infected subjects than in those of uninfected subjects (P <.001). Seroconverters had lower preinfection levels of TRIM5alphahu than did nonseroconverters (P<.001). TRIM5alphahu levels did not change significantly after infection. There was no correlation between TRIM5alphahu levels and viral loads or CD4(+) T cell counts.

Conclusions: High expression of TRIM5alphahu is associated with reduced susceptibility to HIV-1 infection. Furthermore, infection is not associated with disregulation of TRIM5alphahu. TRIM5alphahu expression levels do not contribute to the control of primary HIV-1 viremia.

Publication types

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

MeSH terms

  • Acquired Immunodeficiency Syndrome / genetics*
  • Acquired Immunodeficiency Syndrome / immunology
  • Antiviral Restriction Factors
  • Carrier Proteins / genetics*
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • HIV Seropositivity / genetics
  • HIV-1*
  • Humans
  • Kinetics
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • South Africa
  • Time Factors
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases
  • Viremia / genetics*

Substances

  • Antiviral Restriction Factors
  • Carrier Proteins
  • RNA, Messenger
  • Tripartite Motif Proteins
  • TRIM5 protein, human
  • Ubiquitin-Protein Ligases