HIV-1 CRF10301B近全长基因组遗传特征分析  

Genetic characteristics of HIV-1 CRF103_01B using near full-length genome

作　　者：代漫 李佳[2] 吕诗韵 黄辉煌 刘安[3] 孙丽君[3] 韩梅 李洁[2] 卢红艳[2] 黄春[2] 辛若雷[2] Dai Man;Li Jia;Lyu Shiyun;Huang Huihuang;Liu An;Sun Lijun;Han Mei;Li Jie;Lu Hongyan;Huang Chun;Xin Ruolei(School of Public Health,China Medical University,Shenyang 110122,China;Institute for STD/AIDS Prevention and Treatment,Beijing Center for Disease Prevention and Control,Beijing 100013,China;STD/AIDS Diagnosis and Treatment Center,Beijing You An Hospital,Capital Medical University,Beijing 100069,China;Department of Infectious Diseases,Fifth Medical Center,PLA General Hospital,Beijing 100039,China;Institute for Tuberculosis,Chongqing Public Health Medical Treatment Center,Chongqing 400042,China)

机构地区：[1]中国医科大学公共卫生学院,沈阳110122 [2]北京市疾病预防控制中心性病艾滋病防治所,100013 [3]首都医科大学附属北京佑安医院性病艾滋病诊疗中心,100069 [4]解放军总医院第五医学中心感染病医学部爱心门诊,100039 [5]重庆市公共卫生医疗救治中心结核病研究室,400042

出　　处：《国际病毒学杂志》2022年第3期177-183,共7页International Journal of Virology

基　　金：北京市自然科学基金(7202074);首都卫生发展科研专项(2022-1G-3015);重庆市医学科研项目(2022MSXM149)。

摘　　要：目的描述一株新鉴定的流行重组型HIV-1 CRF103_01B在北京的检出情况,并分析其近全长基因组(near full-length genome,NFLG)遗传特征。方法对2017—2020年北京新诊断或初始抗病毒治疗病例进行HIV-1基因型耐药监测,发现5例疑似感染CRF103_01B毒株。通过逆转录、近末端稀释法,分两段巢式PCR扩增HIV-1 NFLG。获得的序列与分型参考序列进行基因比对,使用MEGA11软件构建邻接法(neighbor-joining,NJ)系统进化树。用SimPlot 3.5软件分析确定基因重组断点,绘制基因组结构图。基于亲本毒株同源NFLG序列比对,挑选较长的重组片段构建NJ进化树,判断可能的亲本毒株来源。用斯坦福大学HIV耐药数据库解析基因型耐药特征。结果共获得5条CRF103_01B NFLG序列,其中4例经男男性行为(men who have sex with men,MSM)感染,1例为女性。与从河北检出的4条CRF103_01B NFLG序列合并分析其重组特征:在CRF01_AE骨架上,gag、pol和nef-3'-LTR基因片段被B亚型重组替换[HXB2 nt 1111±19-1539±16,2531-4478±16(片段Ⅴ),9008±23-9615]。亲本来源分析显示,CRF103_01B的片段Ⅳ与Ⅴ分别与北京B亚型(BJMP3294B)和g5簇CRF01_AE序列(JX112804)聚集成大单系进化簇(bootstrap值分别为97%和100%)。9个CRF103_01B病例均携带非核苷类逆转录酶抑制剂类V106I突变。结论CRF103_01B毒株最可能起源于北京MSM人群,并在北京和河北等地的MSM人群中低水平持续流行,并经异性性途径向一般人群播散。需加强该毒株分子流行病学和耐药监测,关注疾病进展。Objective To elucidate the existence of a novel circulating HIV-1 recombinant form,HIV-1 CRF103_01B in Beijing and to explore its genetic characteristics using the near full-length genome(NFLG).Methods Five individuals were identified as suspect cases of CRF103_01B strain infection in the surveillance of HIV-1 genotypic drug resistance for new diagnosis or antiretroviral therapy in Beijing from 2017 to 2020.The two overlapping segments of HIV-1 genome were amplified by nested PCR with near endpoint dilution method after reverse transcription.The obtained NFLG sequences were aligned with subtyping reference sequences,and neighbor-joining(NJ)phylogenetic tree was constructed using MEGA11.SimPlot 3.5 software was used to determine the breakpoints of recombinant and to draw the map of genome structure.Based on alignment from the homologous NFLG sequences with the putative parental strains,the longer segments were selected to construct the NJ trees,to infer the possible origins of the parental strains.Genotypic drug resistances were interpreted using the Stanford University HIV drug resistance database.Results Five NFLG sequences of CRF103_01B were obtained from four individuals who were infected by men who have sex with men(MSM)and one female.The sequences were analyzed with the four NFLGs of CRF103_01B previously reported in Hebei province to explore the characters of recombination.On the backbone of CRF01_AE,the corresponding segments of gag,pol and nef-3'-LTR gene were substituted by subtype B[HXB2 nt 1111±19-1539±16,2531-4478±16(region Ⅴ),9008±23-9615].Phylogenetic inference analysis showed that regions Ⅳ and Ⅴ of CRF103_01B clustered into large monophyletic clusters with subtype B(BJMP3294B)and g5 CRF01_AE(JX112804)from Beijing,with bootstrap values of 97% and 100%,respectively.All 9 CRF103_01B individuals carried V106I mutation of non-nucleoside reverse transcriptase inhibitor.Conclusions CRF103_01B strain was mostly convinced to be originated from MSM population in Beijing,and continued to circulate

关 键 词：CRF103_01B 近全长基因组 男男性行为 流行重组型 

分 类 号：R373[医药卫生—病原生物学]