title: Effects of human TRIM5alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection.
abstract: TRIM5alpha acts on several retroviruses, including human immunodeficiency virus (HIV-1), to restrict cross-species transmission. Using natural history cohorts and tissue culture systems, we examined the effect of polymorphism in human TRIM5alpha on HIV-1 infection. In African Americans, the frequencies of two non-coding SNP variant alleles in exon 1 and intron 1 of TRIM5 were elevated in HIV-1-infected persons compared with uninfected subjects. By contrast, the frequency of the variant allele encoding TRIM5alpha 136Q was relatively elevated in uninfected individuals, suggesting a possible protective effect. TRIM5alpha 136Q protein exhibited slightly better anti-HIV-1 activity in tissue culture than the TRIM5alpha R136 protein. The 43Y variant of TRIM5alpha was less efficient than the H43 variant at restricting HIV-1 and murine leukemia virus infections in cultured cells. The ancestral TRIM5 haplotype specifying no observed variant alleles appeared to be protective against infection, and the corresponding wild-type protein partially restricted HIV-1 replication in vitro. A single logistic regression model with a permutation test indicated the global corrected P value of <0.05 for both SNPs and haplotypes. Thus, polymorphism in human TRIM5 may influence susceptibility to HIV-1 infection, a possibility that merits additional evaluation in independent cohorts.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Javanbakht
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.forename: Bert
authors.initials: B
authors.lastname: Gold
authors.forename: Desiree C
authors.initials: DC
authors.lastname: Petersen
authors.forename: Colm
authors.initials: C
authors.lastname: O'Huigin
authors.forename: George W
authors.initials: GW
authors.lastname: Nelson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: Susan
authors.initials: S
authors.lastname: Buchbinder
authors.forename: Sharyne
authors.initials: S
authors.lastname: Donfield
authors.forename: Sergey
authors.initials: S
authors.lastname: Shulenin
authors.forename: Byeongwoon
authors.initials: B
authors.lastname: Song
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Perron
authors.forename: Matthew
authors.initials: M
authors.lastname: Stremlau
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
authors.forename: Michael
authors.initials: M
authors.lastname: Dean
authors.forename: Cheryl
authors.initials: C
authors.lastname: Winkler
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D004285:Dogs; D005091:Exons; D005787:Gene Frequency; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000254:growth & development; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007438:Introns; D009052:Leukemia Virus, Murine / Q000254:growth & development; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; D049452:Green Fluorescent Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases