title: Evidence for selection at HIV host susceptibility genes in a West Central African human population.
abstract: BACKGROUND
  HIV-1 derives from multiple independent transfers of simian immunodeficiency virus (SIV) strains from chimpanzees to human populations. We hypothesized that human populations in west central Africa may have been exposed to SIV prior to the pandemic, and that previous outbreaks may have selected for genetic resistance to immunodeficiency viruses. To test this hypothesis, we examined the genomes of Biaka Western Pygmies, who historically resided in communities within the geographic range of the central African chimpanzee subspecies (Pan troglodytes troglodytes) that carries strains of SIV ancestral to HIV-1.
  
  
  RESULTS
  SNP genotypes of the Biaka were compared to those of African human populations who historically resided outside the range of P. t. troglodytes, including the Mbuti Eastern Pygmies. Genomic regions showing signatures of selection were compared to the genomic locations of genes reported to be associated with HIV infection or pathogenesis. In the Biaka, a strong signal of selection was detected at CUL5, which codes for a component of the vif-mediated APOBEC3 degradation pathway. A CUL5 allele protective against AIDS progression was fixed in the Biaka. A signal of selection was detected at TRIM5, which codes for an HIV post-entry restriction factor. A protective mis-sense mutation in TRIM5 had the highest frequency in Biaka compared to other African populations, as did a protective allele for APOBEC3G, which codes for an anti-HIV-1 restriction factor. Alleles protective against HIV-1 for APOBEC3H, CXCR6 and HLA-C were at higher frequencies in the Biaka than in the Mbuti. Biaka genomes showed a strong signal of selection at TSG101, an inhibitor of HIV-1 viral budding.
  
  
  CONCLUSIONS
  We found protective alleles or evidence for selection in the Biaka at a number of genes associated with HIV-1 infection or progression. Pygmies have also been reported to carry genotypes protective against HIV-1 for the genes CCR5 and CCL3L1. Our hypothesis that HIV-1 may have shaped the genomes of some human populations in West Central Africa appears to merit further investigation.
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Il 61801, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Ishida
authors.forename: Taras K
authors.initials: TK
authors.lastname: Oleksyk
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Roca
mesh_terms: D000350:Africa, Central; D000354:Africa, Western; D000619:Aminohydrolases / Q000235:genetics; D000818:Animals; D000090103:Antiviral Restriction Factors; D044383:Black People / Q000208:ethnology / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D044842:Cullin Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D015236:HLA-C Antigens / Q000235:genetics; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D002679:Pan troglodytes / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D000099177:Tsg101 Protein
chemical_list: D000619:Aminohydrolases; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D015236:HLA-C Antigens; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D011991:Receptors, Virus; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D000099177:Tsg101 Protein; C496871:CUL5 protein, human; C106330:CXCR6 protein, human; C477346:TRIM5 protein, human; C529313:APOBEC3H protein, human