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慢性重型乙型肝炎患者血清病毒全长基因特点及其临床意义

黄素园  于德敏  刘峰  陈立  韩悦  李新华  张欣欣 

摘 要:目的 探讨血清HBV全长基因组的准种特性及其与慢性乙型肝炎(CHB)重症化的关系.方法 未接受过抗病毒治疗的CHB、慢性重型乙型肝炎(CSHB)各4例患者,扩增外周血清中HBV全长基因组并克隆、测序,每个标本选取14~16个克隆进行DNA测序及生物信息学分析.计量资料采用独立样本t检验,计数资料采用x2检验.结果 CHB组和CSHB组8例患者共获得120个HBV全长基因组序列.每例患者均为单一基因B型或C型感染.两组全长克隆序列中均发现G1896A突变、A1762T/G1764A、T1753C/G突变,以及前S2区、前S1区起始密码子缺失,CSHB组1例患者还发现A1762T/G1764A/C1766T突变,CSHB组发生一个或多个突变的克隆数占100.0%(60/60),明显多于CHB组的76.7%(46/60)(x2=15.85,P<0.01).在核苷酸和氨基酸水平上,CSHB组的全长基因组、S基因、X基因、P基因和反转录酶编码序列区的准种复杂度和平均遗传距离均比CHB组大,C基因的则比CHB组小,但差异均无统计学意义.结论 慢性重型乙型肝炎患者血清中HBV的各种突变率及准种异质性差异均大于慢性乙型肝炎患者,可能与CHB重症化有关,值得扩大样本进一步研究其临床意义.
关键词:肝炎病毒,乙型;肝炎,乙型,慢性;突变;遗传异质性;重型肝炎;准种


The characterization of serum hepatitis B virus full-length genome in chronic severe hepatitis B patients and its clinical significance

HUANG Su-yuan(Department of Infectious Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)  YU De-min(Department of Infectious Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)  LIU Feng(Department of Infectious Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)  CHEN Li(Department of Infectious Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)  HAN Yue(Department of Infectious Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)  LI Xin-hua(Department of Infectious Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)  ZHANG Xin-xin(Department of Infectious Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China) 

Abstract:Objective To characterize serum hepatitis B virus(HBV)full-length genome quasispecies and to investigate its ralationship with severe exacerbation of chronic hepatitis B(CHB).Methods HBV full-length genome was amplified a

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