TRIM5alpha mediates the postentry block to N-tropic murine leukemia viruses in human cells

Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11827-32. doi: 10.1073/pnas.0403364101. Epub 2004 Jul 27.


Murine leukemia viruses (MLVs) have been classified as N-tropic (N-MLV) or B-tropic (B-MLV), depending on their ability to infect particular mouse strains. The early phase of N-MLV infection is blocked in the cells of several mammalian species, including humans. This block is mediated by a dominant host factor that targets the viral capsid soon after virus entry into the cell has been achieved. A similar block to HIV-1 in rhesus monkey cells is mediated by TRIM5alpha. Here we show that human TRIM5alpha is both necessary and sufficient for the restriction of N-MLV in human cells. Rhesus monkey TRIM5alpha, which potently blocks HIV-1 infection, exhibited only modest inhibition of N-MLV infection. B-MLV was resistant to the antiviral effects of both human and rhesus monkey TRIM5alpha; susceptibility to TRIM5alpha-mediated restriction was conferred by alteration of residue 110 of the B-MLV capsid protein to the amino acid found in the N-MLV capsid. Our results demonstrate that species-specific variation in TRIM5alpha governs its ability to block infection by diverse retroviruses.

Publication types

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

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Antiviral Restriction Factors
  • Carrier Proteins / genetics
  • Carrier Proteins / pharmacology*
  • Carrier Proteins / physiology
  • Cell Line
  • Cyclophilin A / metabolism
  • Dose-Response Relationship, Drug
  • HIV / drug effects
  • HIV / genetics
  • HIV / physiology
  • Humans
  • Infection Control
  • Macaca mulatta
  • Mice
  • Moloney murine leukemia virus / drug effects
  • Moloney murine leukemia virus / physiology*
  • Retroviridae / drug effects
  • Retroviridae / physiology
  • Species Specificity
  • Transfection
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases


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