A rare null allele potentially encoding a dominant-negative TRIM5alpha protein in Baka pygmies.
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.
Torimiro
Judith N
JN
Department of Biochemistry and Physiologic Sciences, Faculty of Medicine and Biomedical Sciences, University of Yaounde I, Yaounde, Cameroon.
Javanbakht
Hassan
H
Diaz-Griffero
Felipe
F
Kim
Jonghwa
J
Carr
Jean K
JK
Carrington
Mary
M
Sawitzke
Julie
J
Burke
Donald S
DS
Wolfe
Nathan D
ND
Dean
Michael
M
Sodroski
Joseph
J
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
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases