A rare null allele potentially encoding a dominant-negative TRIM5α protein in Baka pygmies

Judith N. Torimiro, Hassan Javanbakht, Felipe Diaz-Griffero, Jonghwa Kim, Jean K. Carr, Mary Carrington, Julie Sawitzke, Donald S. Burke, Nathan D. Wolfe, Michael Dean, Joseph Sodroski

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The global acquired immunodeficiency syndrome (AIDS) pandemic is thought to have arisen by the transmission of human immunodeficiency virus (HIV-1)-like viruses from chimpanzees in southeastern Cameroon to humans. TRIM5α is a restriction factor that can decrease the susceptibility of cells of particular mammalian species to retrovirus infection. A survey of TRIM5 genes in 127 indigenous individuals from southeastern Cameroon revealed that approximately 4% of the Baka pygmies studied were heterozygous for a rare variant with a stop codon in exon 8. The predicted product of this allele, TRIM5 R332X, is truncated in the functionally important B30.2(SPRY) domain, does not restrict retrovirus infection, and acts as a dominant-negative inhibitor of wild-type human TRIM5α. Thus, some indigenous African forest dwellers potentially exhibit diminished TRIM5α function; such genetic factors, along with the high frequency of exposure to chimpanzee body fluids, may have predisposed to the initial cross-species transmission of HIV-1-like viruses.

Original languageEnglish (US)
Pages (from-to)140-147
Number of pages8
JournalVirology
Volume391
Issue number1
DOIs
StatePublished - Aug 15 2009

Keywords

  • Africa
  • Cross-species transmission
  • HIV-1
  • Mutant
  • Polymorphism
  • Restriction factor
  • Susceptibility

ASJC Scopus subject areas

  • Virology

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    Torimiro, J. N., Javanbakht, H., Diaz-Griffero, F., Kim, J., Carr, J. K., Carrington, M., Sawitzke, J., Burke, D. S., Wolfe, N. D., Dean, M., & Sodroski, J. (2009). A rare null allele potentially encoding a dominant-negative TRIM5α protein in Baka pygmies. Virology, 391(1), 140-147. https://doi.org/10.1016/j.virol.2009.05.038