Effects of human TRIM5alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection

Virology. 2006 Oct 10;354(1):15-27. doi: 10.1016/j.virol.2006.06.031. Epub 2006 Aug 2.

Abstract

TRIM5alpha acts on several retroviruses, including human immunodeficiency virus (HIV-1), to restrict cross-species transmission. Using natural history cohorts and tissue culture systems, we examined the effect of polymorphism in human TRIM5alpha on HIV-1 infection. In African Americans, the frequencies of two non-coding SNP variant alleles in exon 1 and intron 1 of TRIM5 were elevated in HIV-1-infected persons compared with uninfected subjects. By contrast, the frequency of the variant allele encoding TRIM5alpha 136Q was relatively elevated in uninfected individuals, suggesting a possible protective effect. TRIM5alpha 136Q protein exhibited slightly better anti-HIV-1 activity in tissue culture than the TRIM5alpha R136 protein. The 43Y variant of TRIM5alpha was less efficient than the H43 variant at restricting HIV-1 and murine leukemia virus infections in cultured cells. The ancestral TRIM5 haplotype specifying no observed variant alleles appeared to be protective against infection, and the corresponding wild-type protein partially restricted HIV-1 replication in vitro. A single logistic regression model with a permutation test indicated the global corrected P value of <0.05 for both SNPs and haplotypes. Thus, polymorphism in human TRIM5 may influence susceptibility to HIV-1 infection, a possibility that merits additional evaluation in independent cohorts.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Substitution
  • Animals
  • Antiviral Restriction Factors
  • Black or African American / genetics
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology
  • Cell Line
  • Child
  • Child, Preschool
  • Disease Susceptibility
  • Dogs
  • Exons
  • Gene Frequency
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / genetics
  • HIV Infections / genetics*
  • HIV Infections / immunology*
  • HIV-1 / growth & development
  • Haplotypes
  • Humans
  • Infant
  • Infant, Newborn
  • Introns
  • Leukemia Virus, Murine / growth & development
  • Logistic Models
  • Polymorphism, Single Nucleotide*
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases

Substances

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