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上海市新诊断114例人类免疫缺陷病毒Ⅰ型感染者的分子生物学研究 被引量:17

A molecular epidemiological survey of 114 newly diagnosed HIV-1-infected persons from Shanghai
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摘要 目的对上海市2004至2005年新诊断的114例人类免疫缺陷病毒I型(HIV-I)感染者进行分子流行病学调查,为确定上海市流行的HIV-1的分子生物学特征提供监测依据。方法应用逆转录聚合酶链反应扩增HIV-1多聚酶基因,DNA测序后进行进化系统树分析确定基因亚型并与国际耐药数据库比对辨别耐药性突变位点。结果1.114例中除1例不详外,本市户口33例,占28.95%,外来人口80例,占70.18%;经性传播感染51例,占44.74%,经静脉注射吸毒感染43例,占37.72%,经采供血和输血感染3例,占2.63%,感染途径不详17例,占14.91%;2.基因亚型分别为B亚型9例,占7.89%,B′亚型15例,占13.16%,C亚型1例,占0.88%,G亚型1例,占0.88%,CRF01-AE 38例,占33.33%,CRF07 BC46例,占40.35%和CRF08 BC 4例,占3.51%;3.耐药分析结果表明本次研究人群的耐药性主突变率为18.42%。与蛋白酶抑制剂(PRIs)和逆转录酶抑制剂(RTIs)耐药相关的基因主突变率分别为2.63%(3/114)和17.54%(20/114)。蛋白酶基因主突变位点突变频率为M461,占66.67%.M46L,占33.33%。逆转录酶基因主突变位点突变频率分别为M41L,占7.69%、A62V.占7.69%、F69S.占7.69%、V751/L,占15.38%、K103R,占25.00%、V1181.占23.08%、V179D/E/T,占33.33%、G190R,占8.33%、L210K/M/X,占38.46%、F227L/I,占16.67%、M230R,占8.33%和P236R,占8.33%。结论上海市新诊断的HIV-1感染者依然以静脉吸毒和性传播为主,感染者以外省市流动人门为主。HIV-1基因亚型流行呈多样性,主要以CRF01_AE,CRF07_BC和B/B’为主。在114例新诊断、尚未经抗病毒治疗的HIV-1感染者中,已存在与PRIs和RTIs耐药相关的基因主突变。 Objective To clarify the genetic diversity of HIV-1 strains currently circulating in Shanghai and establish the molecular epidemiological database of HIV-1 infection. Methods The samples from 114 newly diagnosed HIV-1-infected individuals between June 2004 and June 2005 were investigated. HIV-1 pol gene(protease 1-99 aa and reverse transcriptase 1-252 aa) from plasma samples were amplified by RT-PCR, sequenced and phylogenetically analyzed. Protease inhibitors(PRIs) and reverse transcriptase inhibitors (RTIs) resistance-associated mutations in protease (PR) and re- verse transcriptase(RT) regions were analyzed. Results (1)Epidemiological survey showed the existence of different modes of transmission of HIV-1 including sexual contacts 51(44.74 %), intravenous drug users 43 (37.72 % ), contaminated blood/blood products transfusion 3 (2.63 % ) and unknown infection 17(14.91%) ;(2)Phylogenetic analysis revealed that 9 of the analyzed sequences were identified as subtype B(7. 89%), 15 as subtype B'(13. 16%), 1 as subtype C(0. 88%), 1 as subtype G (0.88%), 38asCRF01_AE(33.33%), 46asCRF07 _BC(40.35%) and4 asCRF08 _BC(3.51%); (3)Analysis of drug-resistance associated mutation showed that 21 of 114 (18.42 %) persons infected with drug resistant HIV-1, among which major mutations in PR and RT regions accounted for 2.63% (3/114) and 17.54% (20/114), respectively. The frequencies of major mutation in PR region were M46I(66.67%), M46L(33. 33%) and in RT region were M41L(7.69%), A62V (7.69%), T69S (7.69%), V75I/L(15, 38%), K103R(25.00%), Vl18I(23.08%), V179D/E/T(33.33%), G190R (8.33%), L210K/M/X(38. 46%), 227L/I(16.67%), M230R(8.33%), P236R(8.33% ). Conclusions The results revealed the current presence of multiple HIV-1 subtypes and recombinants strains infecting residents and migrants living in Shanghai. The broad diversity of HIV-1 has been introduced into Shanghai mainly through drug injection and heterosexual contacts. This study also revealed that HIV-1 strains infecting these newly diagnosed treatment-naive persons have acquired major mutations in both PR gene and RT gene of HIV-1.
出处 《中华传染病杂志》 CAS CSCD 北大核心 2006年第5期328-332,共5页 Chinese Journal of Infectious Diseases
基金 上海市医学重点学科建设项目(05111029)
关键词 HIV-1 基因型 重组 遗传 变异(遗传学) HIV-1 Genotype Recombination, genetic Variation(genetics)
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参考文献6

  • 1Zhong P,Kang L,Pan Q,et al.Identification and distribution of HIV type 1 genetic diversity and protease inhibitor resistance-associated mutations in Shanghai,P.R.China.J Acquir Immune Defic Syndr,2003,34:91-101.
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二级参考文献3

  • 1Robertson DL, Sharp PM, McCutchan FE, et al. Recombination in HIV-1.Nature, 1995,374:124-126.
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