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目的研究中国人群CCR5基因开放阅读框架(ORF)区突变并分析其对中国人人类免疫缺陷病毒(HIV)传播和致病的影响。方法研究对象为居住在香港特区的1099名成年中国人,其中785名为HIV阴性健康人,314例为确诊HIV感染的患者。首先对CCR5 ORF进行测序,确定并分析CCR5突变在人群的分布。再对突变G106R、Δ32、R223Q、299(FS)和S3361体外克隆,研究其表达及作为HIV辅助受体功能的改变。结果在CCR5 ORF共检测到10个突变位点。其中7个为有意义突变;突变R223Q是发生频率最高的突变,在正常人是4．7％,在HIV感染者是4．5％;其余CCR5 ORF突变发生频率均＜1％; R223Q位于CCR5膜内区,不影响其作为HIV辅助受体的功能;S336I位于CCR5的C端,同样不影响其功能;突变G106R位于CCR5第3跨膜区,实验显示其辅助受体功能受到明显影响。结论CCR5 ORF突变在中国人群较为常见,一些突变明显影响其作为HIV辅助受体的功能,但在流行病学范围内对HIV感染及致病的影响不明显。
Objective To study the mutation of open reading frame (ORF) region of CCR5 gene in Chinese population and analyze its influence on the transmission and pathogenicity of Chinese human immunodeficiency virus (HIV). METHODS: The study population consisted of 1099 adult Chinese living in the Hong Kong SAR. Of these, 785 were HIV-negative and 314 were confirmed HIV-infected. The CCR5 ORF was first sequenced to determine and analyze the distribution of CCR5 mutations in the human population. The mutated G106R, Δ32, R223Q, 299 (FS) and S3361 were cloned in vitro and their expression and function as HIV co-receptor were studied. Results A total of 10 mutation sites were detected in the CCR5 ORF. Seven of them were meaningful mutations; mutation R223Q was the most frequent mutation in 4.7% of normal subjects and 4.5% of HIV-infected individuals; all other CCR5 ORF mutations were less than 1%; R223Q was located in CCR5 Membrane area, does not affect its function as HIV co-receptor; S336I located in the C terminal of CCR5, the same does not affect its function; mutation G106R located in the third transmembrane region CCR5, the experiment showed that its receptor function was significantly affected. Conclusions The mutation of CCR5 ORF is more common in Chinese population. Some mutations obviously affect its function as HIV co-receptor, but its influence on HIV infection and pathogenicity is not obvious in epidemiology.