乙型肝炎病毒/S型区变异特征及其与乙肝疫苗免疫逃逸的研究  

Characterization of Hepatitis B Virus/S-Gene Mutation and Its Association with Immune Escape of Hepatitis B Vaccine

作　　者：曹阳 贺晓烨 李雯莉[1] 高冉冉[1] 王莹[1] CAO Yang(The First Affiliated Hospital of Xinjiang Medical University,Xinjiang Urumqi 830000,China)

机构地区：[1]新疆医科大学第一附属医院,新疆乌鲁木齐830000 [2]云南省昆明市妇幼健康服务中心基层指导科,云南昆明650000

出　　处：《河北医学》2022年第9期1473-1478,共6页Hebei Medicine

基　　金：新疆维吾尔自治区自然科学基金资助项目,(编号:2021D01C327)。

摘　　要：目的:研究乙型肝炎病毒(HBV)S基因变异特征及其与乙肝疫苗免疫逃逸的关系。方法:选取2021年3月至2022年3月我院1973例住院患者为样本进行横断面研究,均已按照0、1、6月标准程序完成乙肝疫苗(HepB)接种,检测HBV血清标志物和HBV S基因变异情况。结果:1973例患者中HBsAg阳性标本47份(2.38%),年龄>18岁者HBsAg阳性率高于1-18岁人群,父母HBV阴性者HBsAg阳性率低于母亲HBV阳性人群,差异均有统计学意义(P<0.05);与标准序列相比,47份HBsAg阳性标本检出核苷酸突变位点162个,氨基酸突变位点98个,其中a决定簇(aa124-147)内突变位点主要包括I/T126A/N/I/S、Q129H/R、M133L、K141E、T143S、D144A/EH和G145R/A;a决定簇上游(aa99-123)突变位点主要包括Q101R/H、L110I、G112K、S113T/G、S117G和P120Q/R/L;a决定簇下游(aa148-169)突变位点主要包括Y161F/C、E164D、F161Y和R160K;47份HBsAg阳性标本检出氨基酸变异者30份,检出率63.83%,其中19份存在氨基酸极性改变,占63.33%,且有11份发生于a决定簇(aa124-147)内,包括T126I、Q129R、T143S、D144A和G145A等5个变异位点。结论:HBV S基因突变与HepB疫苗免疫逃逸存在密切联系,其中a决定簇(aa124-147)内部T126I、Q129R、T143S、D144A和G145A等位点突变可引起HBsAg极性和亲水性变化,从而导致抗原性下降,造成免疫逃逸发生。Objective:To study the characteristics of hepatitis B virus(HBV)S-gene mutation and its association with immune escape of hepatitis B vaccine.Methods:1,973 inpatients in the hospital between March 2021 and March 2022 were selected as samples for a cross-sectional study.All patients completed hepatitis B(HepB)vaccination according to the standard procedures of 0,1 month and 6 months.HBV serum markers and HBV S-gene mutation were detected.Results:There were 47 HBsAg positive samples among 1973 patients(2.38%),the rate of HBsAg positivity was higher in those aged>18 years than in those aged 1-18 years,and the rate of HBsAg positivity was lower in those with HBV-negative parents than in those with HBV-positive mothers,all with statistically significant differences(P<0.05).Compared with the standard sequence,162 nucleotide mutation sites and 98 amino acid mutation sites were detected in 47 HBsAg-positive samples,among which the mutation sites in the a determinant(aa124-147)mainly included I/T126A/N/I/S,Q129H/R,M133L,K141E,T143S,D144A/EH and G145R/A,mutation sites in the a determinant upstream(aa99-123)were mainly Q101R/H,L110I,G112K,S113T/G,S117G and P120Q/R/L,and mutation sites in the a determinant downstream(aa148-169)mainly included Y161F/C,E164D,F161Y and R160K.Among 47 HBsAg-positive samples,30 samples were found to have amino acid mutation with the detection of 63.83%,among which 19 had amino acid polarity change(according for 63.33%)and 11 occurred in the a determinant(aa124-147),including 5 mutation sites of T126I,Q129R,T143S,D144A and G145A.Conclusion:HBV S-gene mutation is closely associated to the immune escape of HepB vaccine.The mutation sites of T126I,Q129R,T143S,D144A and G145A in the a determinant(aa124-147)can cause changes in the polarity and hydrophilicity of HBsAg,resulting in the decrease of antigenicity and the occurrence of immune escape.

关 键 词：乙型肝炎病毒 疫苗 免疫逃逸 基因突变 A决定簇 抗原性 

分 类 号：R512.62[医药卫生—内科学]