中华微生物学和免疫学杂志
中華微生物學和免疫學雜誌
중화미생물학화면역학잡지
CHINESE JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY
2008年
3期
258-263
,共6页
张晓丽%韩晓旭%代娣%董西华%包名家%赵彬%姜拥军%王亚男%张子宁%周立平%尚红
張曉麗%韓曉旭%代娣%董西華%包名傢%趙彬%薑擁軍%王亞男%張子寧%週立平%尚紅
장효려%한효욱%대제%동서화%포명가%조빈%강옹군%왕아남%장자저%주립평%상홍
人类免疫缺陷病毒1%gp41%中和抗体表位%2F5%4E10
人類免疫缺陷病毒1%gp41%中和抗體錶位%2F5%4E10
인류면역결함병독1%gp41%중화항체표위%2F5%4E10
HIV-1%gp41%Neutralizing epitope%2F5%4E10
目的 探讨92例HIV/AIDS患者HIV-1病毒近膜端(membrane proximal external re-gion,MPER)中和抗体2F5和4E10保守表位ELDKWA、NWFDIT氨基酸变异特点,为中国HIV/AIDS患者免疫治疗以及疫苗设计提供数据.方法 Nest-PCR扩增HIV-1 env区gp41段基因,核酸序列测定,翻译为氨基酸与HIV-1 Sequence Database HXB Ⅱ参考株中和抗体表位数据比对,分析2F5、4E10中和表位氨基酸变异情况.结果 92例HIV/AIDS患者HIV-1外膜蛋白env gp41段中和抗体2F5、4E10保守表位氨基酸均存在突变;2F5中和抗体表位主要有E662A(14.1%)、K665S(17.4%)、A667K(16.3%)突变;4E10中和抗体表位主要有N671S(13.0%)、D674S(3.3%)、T676S(16.3%)突变;CRF_B'C亚型与B'亚型的2F5和4E10表位氨基酸突变差异具有统计学意义(P<0-05);CRF_B'C与CRF01_AE亚型2F5表位突变差异具有统计学意义(P<0.05);B'亚型缓慢进展者、HIV感染者和AIDS患者的4E10表位氨基酸突变差异具有统计学意义(P<0.05).结论 92例HIV/AIDS患者HIV.1包膜蛋白env gp41段中和抗体2F5、4E10中和表位氨基酸存在突变,且变异多样化;不同亚型中和抗体保守表位氨基酸位点变异有差异;B'亚型4E10中和抗体表位变异可能与疾病进展有一定联系.
目的 探討92例HIV/AIDS患者HIV-1病毒近膜耑(membrane proximal external re-gion,MPER)中和抗體2F5和4E10保守錶位ELDKWA、NWFDIT氨基痠變異特點,為中國HIV/AIDS患者免疫治療以及疫苗設計提供數據.方法 Nest-PCR擴增HIV-1 env區gp41段基因,覈痠序列測定,翻譯為氨基痠與HIV-1 Sequence Database HXB Ⅱ參攷株中和抗體錶位數據比對,分析2F5、4E10中和錶位氨基痠變異情況.結果 92例HIV/AIDS患者HIV-1外膜蛋白env gp41段中和抗體2F5、4E10保守錶位氨基痠均存在突變;2F5中和抗體錶位主要有E662A(14.1%)、K665S(17.4%)、A667K(16.3%)突變;4E10中和抗體錶位主要有N671S(13.0%)、D674S(3.3%)、T676S(16.3%)突變;CRF_B'C亞型與B'亞型的2F5和4E10錶位氨基痠突變差異具有統計學意義(P<0-05);CRF_B'C與CRF01_AE亞型2F5錶位突變差異具有統計學意義(P<0.05);B'亞型緩慢進展者、HIV感染者和AIDS患者的4E10錶位氨基痠突變差異具有統計學意義(P<0.05).結論 92例HIV/AIDS患者HIV.1包膜蛋白env gp41段中和抗體2F5、4E10中和錶位氨基痠存在突變,且變異多樣化;不同亞型中和抗體保守錶位氨基痠位點變異有差異;B'亞型4E10中和抗體錶位變異可能與疾病進展有一定聯繫.
목적 탐토92례HIV/AIDS환자HIV-1병독근막단(membrane proximal external re-gion,MPER)중화항체2F5화4E10보수표위ELDKWA、NWFDIT안기산변이특점,위중국HIV/AIDS환자면역치료이급역묘설계제공수거.방법 Nest-PCR확증HIV-1 env구gp41단기인,핵산서렬측정,번역위안기산여HIV-1 Sequence Database HXB Ⅱ삼고주중화항체표위수거비대,분석2F5、4E10중화표위안기산변이정황.결과 92례HIV/AIDS환자HIV-1외막단백env gp41단중화항체2F5、4E10보수표위안기산균존재돌변;2F5중화항체표위주요유E662A(14.1%)、K665S(17.4%)、A667K(16.3%)돌변;4E10중화항체표위주요유N671S(13.0%)、D674S(3.3%)、T676S(16.3%)돌변;CRF_B'C아형여B'아형적2F5화4E10표위안기산돌변차이구유통계학의의(P<0-05);CRF_B'C여CRF01_AE아형2F5표위돌변차이구유통계학의의(P<0.05);B'아형완만진전자、HIV감염자화AIDS환자적4E10표위안기산돌변차이구유통계학의의(P<0.05).결론 92례HIV/AIDS환자HIV.1포막단백env gp41단중화항체2F5、4E10중화표위안기산존재돌변,차변이다양화;불동아형중화항체보수표위안기산위점변이유차이;B'아형4E10중화항체표위변이가능여질병진전유일정련계.
Objective To study the amino acid mutations in neutralizing antibody 2F5 and 4E10 conserved epitopes ELDKWA and NWFDIT of HIV-1 membrane proximal external region(MPER)in 92 HIV-infected individuals and AIDS patients in China,and to provide a basis for the neutralizing antobodies immunotherapy and a design of vaccines. Methods Nest-PCR methods were used to amplity genes of the HIV-1 env gp41 region.The amplified fragments were sequenced by double-deoxygen terminal method and translated into amino acids for analysis.The mutations of 2F5 and 4E10 neutralizing epitopes were identified by comparison with the epitopes reference data in HIV-1 Sequence Database.Results There were mutations on both 2F5 and 4E10 neutralizing epitopes.2F5 conserved neutralizing epitopes major mutations tocused on E662A(14.1%),K665S(17.4%),A667K(16.3%),and 4E10 conserved neutralizing epltopes major mutations included N671S(13.0%),D674S(3.3%),T676S(16.3%).The mutation rates of 2F5 and 4E10 epitopes were significanfly different between CRF_B'C-clade and B'-clade(P<0.05).The mutata rates of CRF_B'C-clade were higher than that of CRFOI_AE-clade in 2F5 epitopes(P<0.05).The mutation rates of B'-clade in 4E10 eiptopes showed significant difference in slow progressors,HIV-infected individuals and AIDS patients,respectively(P<0.05).Conclusion The HIV-1 patients in China are demonstrated diversified mutations in 2F5 and 4E10 neutralizing epitopes.The mutation degrees of amlno acids in conserved neutralizing epitopes are different in different subtypes.There may be a correlation between neutralizing epitopes mutations of 4E10 with disease progression.
