云南省艾滋病主要流行地区人类免疫缺陷病毒1型毒株 gag基因的变异特征  

Variation characteristics of gag gene of human immunodeficiency virus type 1 strain in the main epidemic areas of acquired immunodeficiency syndrome in Yunnan Province

作　　者：李健健 邱钰婷 刘家法 王佳丽 张米 董兴齐 Li Jianjian;Qiu Yuting;Liu Jiafa;Wang Jiali;Zhang Mi;Dong Xingqi(Clinical Laboratory,Yunnan Provincal Infectious Diseases Hospital/AIDS Care Center,Kunming 650301,China;School of Public Health,Kunming Medical University,Kunming 650000,China)

机构地区：[1]云南省传染病医院/艾滋病关爱中心检验科,昆明650301 [2]昆明医科大学公共卫生学院,昆明650000

出　　处：《中华传染病杂志》2022年第5期281-287,共7页Chinese Journal of Infectious Diseases

基　　金：国家自然科学基金地区基金(81960605);云南省高层次卫生技术人才培养经费资助项目(H-2018050);云南省艾滋病病毒学及临床诊疗技术创新研究中心(202102AA310005);昆明医科大学2021年硕士研究生创新基金(2021S009)。

摘　　要：目的调查云南省4个艾滋病主要流行地区人类免疫缺陷病毒1型(human immunodeficiency virus type 1, HIV-1)毒株gag基因序列的变异特征。方法利用完全随机抽样法抽取2019年1月至2020年12月云南省昆明市、德宏傣族景颇族自治州、红河哈尼族彝族自治州和临沧市抗病毒治疗定点机构进行随访治疗的480例人类免疫缺陷病毒(human immunodeficiency virus, HIV)感染/艾滋病患者, 收集其流行病学信息, 采集血浆标本后送至云南省传染病医院进行分析, 采用巢式聚合酶链反应扩增HIV-1gag基因, 并进行基因分型, 采用MEGA 6.06软件构建系统进化树, 采用VESPA在线分析工具分析特征性氨基酸, 采用Distance程序计算gag, 以及gag蛋白不同区段的基质蛋白p17、衣壳蛋白p24、核衣壳蛋白p7及p6蛋白的基因距离。采用SNAP程序分析同义突变频率与非同义突变频率比值(Ks/Ka值)。多组间统计学比较采用方差分析。结果 404例患者成功获得gag基因序列, 其中以男性居多(250例, 61.9%), 年龄为40~59岁者占59.7%(241/404), 传播途径主要为异性性传播(61.4%, 248/404)。主要流行的HIV-1亚型依次为流行重组型(circulating recombinant form, CRF)08C 155例(38.4%), CRF01E 74例(18.3%), 独特重组型(unique rebombinant form, URF)52例(12.9%)、CRF07C 39例(9.7%), C亚型34例(8.4%), 其他亚型28例(6.9%), B亚型22例(5.4%)。构建系统进化树发现, CRF08C亚型形成了2个主要传播簇, 2个传播簇间共有8个位点的特征性氨基酸分布存在显著差异, 分别为第79、93、121、122、151、363、395和396位点。CRF01E、CRF07C和CRF08C的gag基因距离分别为0.090±0.004、0.088±0.004和0.078±0.002, 差异有统计学意义(F=118.33, P<0.001)。3种主要亚型中, gag区段的Ks/Ka值分别为4.003±1.309、4.141±0.860和4.514±1.215, 差异有统计学意义(F=1.35, P<0.001);p17区段的Ks/Ka值分别为2.590±0.186、2.831±0.496和2.936±0.475, 差异有统计学意义(F=1.59, Objective To analyze the variation characteristics of gag gene sequence of human immunodeficiency virus type 1(HIV-1)epidemic strains in four major acquired immunodeficiency syndrome(AIDS)endemic areas in Yunnan Province.Methods A total of 480 human immunodeficiency virus(HIV)/AIDS patients from designated antiviral treatment institutions in Kunming City,Dehong Dai and Jingpo Autonomous Prefecture,Hani-Yi Autonomous Prefecture of Honghe and Lincang City in Yunnan Province from January 2019 to December 2020 were randomly selected.The epidemiological information of the patients was collected.The plasma samples were collected and sent to the Yunnan Provincial Infectious Diseases Hospital for analysis.HIV-1 gag gene was amplified by nested polymerase chain reaction for genotyping.The phylogenetic tree was constructed by MEGA 6.06,and the characteristic amino acids were analyzed by VESPA online analysis tool.The gene distances of gag and matrix protein p17,capsid protein p24,nucleocapsid protein p7 and p6 protein of gag protein were calculated by Distance program.The ratio of synonymous mutation frequnency and non-synonymous mutation frequnency(Ks/Ka)was analyzed by SNAP program.Statistical comparison among multiple groups was performed using analysis of variance.Results The gag gene sequences were successfully obtained from 404 patients.Most of these patients were men(250 cases,61.9%),59.7%(241/404)of patients were aged 40 to 59 years,and the main transmission route was heterosexual transmission(61.4%,248/404).The main epidemic subtypes of HIV-1 were circulating recombinant form(CRF)08_BC(38.4%,155/404),CRF01_AE(18.3%,74/404),unique recombinant form(URF)(12.9%,52/404),CRF07_BC(9.7%,39/404),C subtype(8.4%,34/404),other subtypes(6.9%,28/404)and B subtype(5.4%,22/404).Two main spreading clusters were formed by CRF08_BC in the phylogenetic tree,and there were significant differences in the distribution of characteristic amino acids of eight loci between the two spreading clusters,including No.79,93,121,122,151,363,395 an

关 键 词：HIV-1 亚型 传播簇 遗传变异 

分 类 号：R512.91[医药卫生—内科学]