APOBEC3G genetic variants and their influence on the progression to AIDS
APOBEC3G genetic variants and their influence on the progression to AIDS
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DOI：
10.1128/jvi.78.20.11070-11076.2004
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发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Winkler, CA
中科院分区：
文献类型：
--
作者：
An, P;Bleiber, G;Winkler, CA
胞嘧啶脱氨酶APOBEC 3G在缺乏人类免疫缺陷病毒1型（HIV-1）辅助基因HIV-1病毒感染因子（vif）的情况下，通过在新合成的HIV-1 DNA负链中引入G->A超突变来抑制病毒复制。我们检验了APOBEC 3G的遗传变异可能改变HIV-1传播和疾病进展的假设。在启动子区（3个）、内含子（2个）和外显子（2个）中发现了单核苷酸多态性。确定了6个HIV-AIDS前瞻性队列中3，073名研究参与者的基因型。一个密码子改变变体，外显子4中的H186 R，在非洲裔美国人（AA）中是多态性的（f = 37%），在欧洲裔美国人（f < 3%）或欧洲人（f = 5%）中是罕见的。对于AA，变异等位基因186 R与CD 4 T细胞的下降强烈相关（平方根尺度上的CD 4斜率：-1.86，P = 0.009）。186 R等位基因还与AA中加速进展为AIDS定义条件相关。186 R酶的体外抗病毒活性不劣于常见的H186变体。这些研究表明，APOBEC 3G变异体可能对HIV-1疾病进展具有修饰作用，值得进一步研究。
The cytosine deaminase APOBEC3G, in the absence of the human immunodeficiency virus type 1 (HIV-1) accessory gene HIV-1 viral infectivity factor (vif), inhibits viral replication by introducing G-->A hypermutation in the newly synthesized HIV-1 DNA negative strand. We tested the hypothesis that genetic variants of APOBEC3G may modify HIV-1 transmission and disease progression. Single nucleotide polymorphisms were identified in the promoter region (three), introns (two), and exons (two). Genotypes were determined for 3,073 study participants enrolled in six HIV-AIDS prospective cohorts. One codon-changing variant, H186R in exon 4, was polymorphic in African Americans (AA) (f = 37%) and rare in European Americans (f < 3%) or Europeans (f = 5%). For AA, the variant allele 186R was strongly associated with decline in CD4 T cells (CD4 slope on square root scale: -1.86, P = 0.009), The 186R allele was also associated with accelerated progression to AIDS-defining conditions in AA. The in vitro antiviral activity of the 186R enzyme was not inferior to that of the common H186 variant. These studies suggest that there may be a modifying role of variants of APOBEC3G on HIV-1 disease progression that warrants further investigation.