四川省两县(区)乙型肝炎病毒S基因和P基因变异分析

Analysis on Mutation of S gene and P gene of Hepatitis B Virus in Two Counties of Sichuan Province

目的分析四川省两县(区)乙型肝炎(乙肝)病毒(Hepatitis B Virus,HBV)S基因和P基因变异。方法从乙肝病毒表面抗原、乙肝病毒e抗原均阳性的血清中提取病毒脱氧核糖核酸,经聚合酶链反应和核苷酸测序后,比较和分析S基因和P基因核苷酸和氨基酸变异。结果47例慢性HBV感染者血清标本中,12份标本在"a"决定簇内出现氨基酸变异(25.53%),分别为T126A、I126T/S、P127T、T131N、M133L、M133T、T140I;变异主要集中在"a"决定簇的第1环上(92.86%,13/14)。1份标本逆转录酶C域中出现rtV207I变异。结论自然发生的氨基酸变异主要集中在"a"决定簇的第1环上,其抗原性已改变,对乙肝疫苗接种人群构成了潜在的威胁。拉米夫定耐药株也可在未接受核苷(酸)类药物治疗的病人中发现。

Objective To analyze HBV S gene/P gene mutation in 2 counties（districts）of Sichuan province. Methods HBV DNA were extracted from sera positive both for HBsAg and HBeAg. After PCR and nucleotide sequencing, nucleotide/amino acid mutation in S and P gene were compared and analyzed. Results Of 47 serum samples from patients with chronic HBV infection,amino acid mutation in ‘a’ determinant occurred in 12 samples（25.53%, 12/47）,correla- ting with T126A, I126T/S, P127T, T131N, M133L, M133T and T140I; high proportion of mutation clustered in first loop of ‘a’ determinant（92.86% ,13/14）,rtV207I mutation in C domain of reverse transcription occured in one sample. Conclusion Naturally occurring mutation in ‘a ’ determinant clustered predominantly in the first loop and usually associated with altered antigenicity,posing a potential threat to successfully vaccinated individuals; Lamivudine-resistant mutant might occur in patient even without nucleotide analogue treatment.