复旦大学：《传染病学 Infectious diseases》课程教学资源（课件讲稿）病毒性肝炎 Viral hepatitis

Viral hepatitis Jiming Zhang(张继明),MD Professor of medicine Department of Infectious Diseases Huashan Hospital, Fudan University

Viral Hepatitis Jiming Zhang (张继明）, M.D. Professor of Medicine Department of Infectious Diseases Huashan Hospital, Fudan University 1

张继明教授简介 复旦大学附属华山医院主任医师,教授,博士研究生导师 教育部与卫生部医学分子病毒学重点实验室双聘教授 华山医院肝病研究室主任,感染病科副主任 华山医院药物临床试验机构肝病专业组组长 2011年度“复旦大学优秀研究生导师” 上海市病毒学分会主任委员 上海市肝病学分会委员、内科学分会委员 研究方向为慢性乙肝的发病机制、乙型肝炎病毒耐药变异等 目前承担国家级课题7项 E-mai l: jmzhang@fudan edu cn

复旦大学附属华山医院主任医师，教授，博士研究生导师 教育部与卫生部医学分子病毒学重点实验室双聘教授 华山医院肝病研究室主任，感染病科副主任 华山医院药物临床试验机构肝病专业组组长 2011年度“复旦大学优秀研究生导师” 上海市病毒学分会主任委员 上海市肝病学分会委员、内科学分会委员 研究方向为慢性乙肝的发病机制、乙型肝炎病毒耐药变异等 目前承担国家级课题7项 E-mail: jmzhang@fudan.edu.cn 张继明教授简介

Definition Viral hepatitis is a group systemic infection affecting the liver predominantly caused by 5 kinds of viruses at least Five hepatotropic hepatitis viruses are responsible for the vast majority of hepatitis cases(classical Hepatitis a virus(HAv) Hepatitis B virus(HBv) Hepatitis C virus(HCv Hepatitis d or delta virus(hDv Hepatitis E virus(HEv)

Definition • Viral hepatitis is a group systemic infection affecting the liver predominantly caused by 5 kinds of viruses at least • Five hepatotropic hepatitis viruses are responsible for the vast majority of hepatitis cases(classical) : Hepatitis A virus (HAV) Hepatitis B virus (HBV) Hepatitis C virus (HCV) Hepatitis D or delta virus (HDV) Hepatitis E virus (HEV) 3

The pathogen

The pathogen 4

Hepatitis a virus a positive-stranded rna genome approximately 7.5 kb long At least 4 different hav genotypes(l, ll, Ill, and Vil) Only one antigen-antibody system °Ant-HA∨ Igm is diagnostic evidence of recent infection Igg is protective antibody

Hepatitis A Virus • A positive-stranded RNA genome approximately 7.5 kb long • At least 4 different HAV genotypes ( I, II, III, and VII) • Only one antigen-antibody system. • Anti-HAV IgM is diagnostic evidence of recent infection • IgG is protective antibody 5

Hepatitis b virus HBV is a kind of hepadnavirus Three particles in serum two types of non-infectious particles spherical particles and filamentous forms, composed of Surface antigen(HBsag) Dane particle: infectious particles °10 genotypes

Hepatitis B virus • HBV is a kind of hepadnavirus • Three particles in serum: two types of non-infectious particles: spherical particles and filamentous forms, composed of Surface antigen (HBsAg) Dane particle: infectious particles • 10 genotypes 6

HBV genome and open reading frames Hepatitis b virion genome is a small circular, partially double stranded dNA with 3. 2kb long Four open reading frames(ORF) coded on the minus strand: C, S, X, and p region S regions: encode pre-s1, pre-S2 and HBSAg C region included pre-C and c gene, encode HBeAg and HBCAg X region encodes HBxAg P region encodes dNA polymerase

HBV genome and open reading frames  Hepatitis B virion genome is a small circular, partially double stranded DNA with 3.2kb long.  Four open reading frames (ORF) coded on the minus strand: C, S, X, and P region: S regions: encode pre-s1, pre-s2 and HBsAg. C region included pre-C and C gene, encode HBeAg and HBcAg X region encodes HBxAg P region encodes DNA polymerase

Hepatitis B Virus Dane particle and genome HBV HBsA HBCA DNA Polymerase Partially double-stranded DNA HBeAg( circulating form OOOOOO Partially double-stranded circular dna virus A member of the Hepadnaviridae

8 Hepatitis B Virus Dane Particle and Genome HBsAg HBcAg Partially double-stranded DNA HBeAg (circulating form) DNA Polymerase  Partially double-stranded circular DNA virus  A member of the Hepadnaviridae HBV

Hepatitis B Genome HBSA 13 Polymerase erase Partially double stranded HBeA form Partially double-stranded circular dna virus A member of the Hepadnaviridae 1816 Chen WN, Oon CJ. FEBS Letters 453 237-242(1999) HBcAg Hunt, et al., Hepatology, 31, 5, 1037-1044(2000) HBeA g Lee WM. The New England Journal of Medicine 337,24,1733-1745(1997)

9 Hepatitis B Genome HBcAg, HBeAg Polymerase HBsAg • Partially double-stranded circular DNA virus • A member of the Hepadnaviridae Chen WN, Oon CJ. FEBS Letters 453 237-242 (1999) Hunt, et al., Hepatology, 31, 5, 1037-1044 (2000) Lee WM. The New England Journal of Medicine, 337, 24, 1733-1745 (1997) HBsAg HBcAg Polymerase Partially double stranded DNA HBeAg circulating form

Three particles in serum a8 10 1010 1013

Three particles in serum