上海地区HIV毒株基因亚型分布及原发基因耐药的分子流行病学研究

刘莉1; 马建新1; 郑毓芳1; ,张仁芳1; 沈银忠1; 李莉1; 陈军1,王珍燕1; 孙富艳1; 卢洪洲1,2,3

微生物与感染 ›› 2011, Vol. 6 ›› Issue (1) : 4-10.

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微生物与感染 ›› 2011, Vol. 6 ›› Issue (1) : 4-10.
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上海地区HIV毒株基因亚型分布及原发基因耐药的分子流行病学研究

  • 刘莉1; 马建新1; 郑毓芳1; ,张仁芳1; 沈银忠1; 李莉1;  陈军1,王珍燕1; 孙富艳1; 卢洪洲1,2,3
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Molecular Epidemiology of HIV-1 Subtypes and Primary Drug Resistant Strains in Shanghai

  • LIU Li1; MA Jian-Xin1; ZHENG Yu-Fang1; ZHANG Ren-Fang1; SHEN Yin-Zhong1; LI Li1; CHEN Jun1; WANG Zhen-Yan1; SUN Fu-Yan1; LU Hong-Zhou1,2,3
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摘要

本文通过对未经抗病毒治疗患者的人类免疫缺陷病毒1型(HIV-1)毒株进行检测,了解上海地区HIV-1的亚型分布及原发耐药基因变异现状。对118例未经治疗的HIV感染者其标本中HIV蛋白酶全长和部分反转录酶基因进行反转录-聚合酶链反应(RT-PCR)扩增,经DNA测序后进行系统进化树分析和重组分析,以确定HIV-1基因亚型和重组体,并与斯坦福耐药数据库比对,了解耐药性突变位点。使用斯坦福REGA HIV亚型分型工具和美国国立生物技术信息中心(NCBI)HIV亚型分析工具分析亚型,获得118例患者的HIV基因序列,基因分型分别为CRF01_AE重组体57例(48.3%)、B亚型36例(30.5%)、CRF07_BC 15例 (12.7%)、CRF08_BC 7例(5.9%)、C亚型2例(1.7%),亚型间或重组体间二重重组体(B/CRF01_A E)1例(0.8%)。蛋白酶抑制剂(PI)和反转录酶抑制剂相关的耐药基因突变率达54.2%(64/118),其中2例(1.7%)发生PI耐药,基因突变位点:M46L、Q58E。5例(4.1%)对反转录酶抑制剂产生耐药,其中对核苷类反转录酶抑制剂(NRTI)和非核苷类反转录酶抑制剂(NNRTI)的耐药率分别为3例(2.4%)和5例(4.1%)。基因突变位点:NRTI为M41L、D67N、T69I/N/S、K70L、L74V、V75L、V118I、M184V、L210W/F/M/S和T215F;NNRTI为V90I、L100V、K103R/N、V106M/P/I/G、E138G/A、V179E/D/T、Y181C、G190A、H221Y、F227L、K238S和Y318F。结果提示,上海地区HIV毒株以CRF01_AE重组亚型为主,且发现新的重组体,可能出现新重组体流行的趋势。PI和反转录酶抑制剂相关的耐药基因突变率较高,且存在高度原发耐药毒株,应加强HIV-1耐药基因变异监测,科学、合理地给予抗病毒治疗。

Abstract

To better understand the genetic diversity and drug resistance-associated mutations of human immunodeficiency virus type 1 (HIV-1) strains isolated from 118 drug-naive individuals in Shanghai. pol genes of the patients were amplified by nest reverse transcriptase-polymerase chain reaction (RT-PCR) and nucleotide sequence. REGA HIV-1 Subtyping Tool and National Center for Biotechnology Information (NCBI) HIV Subtyping Tool were used to identify the subtypes of obtained sequences. Drug-resistance-associated mutations in protease and reverse transcriptase regions were analyzed with Stanford University HIV Drug Resistance Database. The results showed that CRF01_AE predominated in Shanghai with 48.3%, followed by subtype B (30.5%), CRF07_BC (12.7%), CRF08_BC (5.9%), and C (1.7%). Besides, one inter-subtype and inter-CRF recombinants B/CRF01_AE (0.8%) was detected. Protease inhibitor-associated primary resistance mutations were found in 2 (1.7%) cases: M46L and Q58E each. The mutations conferring primary resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were detected in 3 (2.4%) and 5 (4.1%), respectively (NRTI: M41L、D67N、T69I/N/S、K70L、L74V、V75L、V118I、M184V、L210W/F/M/S and T215F;NNRTI: V90I、L100V、K103R/N、V106M/P/I/G、E138G/A、V179E/D/T、Y181C、G190A、H221Y、F227L、K238S和Y318F). This study reveals that CRF01_AE predominates in Shanghai. Antiretroviral drug resistance among untreated HIV-1-infected individuals is 5.9%. The monitoring of HIV-1 drug resistance mutations should be paid more attention. Acquired immunodeficiency syndrome (AIDS) patients should take drug resistance test before antiretroviral therapy in future.

关键词

人类免疫缺陷病毒 / 基因亚型 / 重组体 / 耐药基因突变

Key words

Human immunodeficiency virus / Subtyping / Recombinant form / Mutation in drug resistance gene

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刘莉1; 马建新1; 郑毓芳1; ,张仁芳1; 沈银忠1; 李莉1; 陈军1,王珍燕1; 孙富艳1; 卢洪洲1,2,3. 上海地区HIV毒株基因亚型分布及原发基因耐药的分子流行病学研究[J]. 微生物与感染. 2011, 6(1): 4-10
LIU Li1; MA Jian-Xin1; ZHENG Yu-Fang1; ZHANG Ren-Fang1; SHEN Yin-Zhong1; LI Li1; CHEN Jun1; WANG Zhen-Yan1; SUN Fu-Yan1; LU Hong-Zhou1,2,3. Molecular Epidemiology of HIV-1 Subtypes and Primary Drug Resistant Strains in Shanghai[J]. Journal of Microbes and Infections. 2011, 6(1): 4-10

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