An HIV-1 resistance polymorphism in TRIM5α gene among Chinese intravenous drug users.
BACKGROUND
TRIM5α has species-specific restriction activity against replication of many retroviruses, including HIV-1. Though human also express TRIM5α protein, it is less potent in suppressing infection of HIV-1 than most orthologs of other nonhuman primates. Previous association studies suggested that polymorphisms in TRIM5α gene might protect against HIV-1 infection. However, the exact variation accounting for this protective effect was not certain.


METHODS
One thousand two hundred ninety-four Chinese intravenous drug users (IDUs), including 1011 Hans and 283 Dai subjects, were investigated for sequence variations in TRIM5α and association with HIV-1 resistance. Resequencing of the putative functional domains in exon2 and exon8 was carried out in 1151 subjects, along with exon2 resequencing in a further 143 HIV-1-infected IDUs.


RESULTS
We identified 14 different nucleotide variants, including 4 with minor allele frequency >0.05. We observed that the frequency of 43Y homozygote in seronegative IDUs was significantly higher than that in the HIV-1-infected IDUs, suggesting a protective effect among the homozygote subjects [odds ratio (95% confidence interval) = 0.46 (0.22 to 0.94), P = 0.033, Mantel-Haenszel test].


CONCLUSIONS
we concluded that H43Y might account for the HIV-1 resistance due to TRIM5α gene in Chinese IDUs.
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
Feng-Liang
FL
Liu
Yu-Qing
YQ
Qiu
Hong
H
Li
Yi-Qun
YQ
Kuang
Xia
X
Tang
Guang
G
Cao
Nelson Leung Sang
NL
Tang
Yong-Tang
YT
Zheng
D000293:Adolescent; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D000090103:Antiviral Restriction Factors; D044466:Asian People; D002352:Carrier Proteins / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D015819:Substance Abuse, Intravenous; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D055815:Young Adult
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases