title: A rare null allele potentially encoding a dominant-negative TRIM5alpha protein in Baka pygmies.
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. TRIM5alpha 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 TRIM5alpha. Thus, some indigenous African forest dwellers potentially exhibit diminished TRIM5alpha 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.
authors: Department of Biochemistry and Physiologic Sciences, Faculty of Medicine and Biomedical Sciences, University of Yaounde I, Yaounde, Cameroon.
authors: Judith N
authors: JN
authors: Torimiro
authors: Hassan
authors: H
authors: Javanbakht
authors: Felipe
authors: F
authors: Diaz-Griffero
authors: Jonghwa
authors: J
authors: Kim
authors: Jean K
authors: JK
authors: Carr
authors: Mary
authors: M
authors: Carrington
authors: Julie
authors: J
authors: Sawitzke
authors: Donald S
authors: DS
authors: Burke
authors: Nathan D
authors: ND
authors: Wolfe
authors: Michael
authors: M
authors: Dean
authors: Joseph
authors: J
authors: Sodroski
mesh_terms: D000483:Alleles; D000090103:Antiviral Restriction Factors; D044383:Black People / Q000235:genetics*; D002163:Cameroon; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D005091:Exons; D005838:Genotype; D015658:HIV Infections / Q000235:genetics; D006801:Humans; D017422:Sequence Analysis, DNA; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases