The Cytoplasmic Body Component TRIM5alpha Restricts HIV-1 Infection in Old World Monkeys

Nature. 2004 Feb 26;427(6977):848-53. doi: 10.1038/nature02343.

Abstract

Host cell barriers to the early phase of immunodeficiency virus replication explain the current distribution of these viruses among human and non-human primate species. Human immunodeficiency virus type 1 (HIV-1), the cause of acquired immunodeficiency syndrome (AIDS) in humans, efficiently enters the cells of Old World monkeys but encounters a block before reverse transcription. This species-specific restriction acts on the incoming HIV-1 capsid and is mediated by a dominant repressive factor. Here we identify TRIM5alpha, a component of cytoplasmic bodies, as the blocking factor. HIV-1 infection is restricted more efficiently by rhesus monkey TRIM5alpha than by human TRIM5alpha. The simian immunodeficiency virus, which naturally infects Old World monkeys, is less susceptible to the TRIM5alpha-mediated block than is HIV-1, and this difference in susceptibility is due to the viral capsid. The early block to HIV-1 infection in monkey cells is relieved by interference with TRIM5alpha expression. Our studies identify TRIM5alpha as a species-specific mediator of innate cellular resistance to HIV-1 and reveal host cell components that modulate the uncoating of a retroviral capsid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cloning, Molecular
  • Cytoplasmic Structures / chemistry*
  • Cytoplasmic Structures / metabolism
  • Disease Susceptibility*
  • Genetic Variation / genetics
  • HIV Infections / metabolism*
  • HIV Infections / veterinary
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • HeLa Cells
  • Humans
  • Macaca mulatta / genetics
  • Macaca mulatta / metabolism*
  • Macaca mulatta / virology*
  • Molecular Sequence Data
  • Mutation / genetics
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • Simian Immunodeficiency Virus / physiology
  • Species Specificity
  • Ubiquitin-Protein Ligases
  • Virus Replication

Substances

  • Protein Isoforms
  • Proteins
  • TRIM5(alpha) protein, rhesus monkey
  • Ubiquitin-Protein Ligases

Associated data

  • RefSeq/NM_033034
  • RefSeq/NM_033092