Hepatitis viruses

5 hepatitis viruses: Hepatitis A virus(HAV) Hepatitis B virus(HBV) Hepatitis C virus(HCV) Hepatitis D virus(HDV) Hepatitis E virus(HEV)

Characteristic properties of hepatitis item HAV HBV HCV HDV HEV Classification Picorna- viridae Hepadnaviridae Flavi-v iridae Defective virus Caliciviridae Diameter(nm) 27 42 36-62 36 32 Nucleic acid +ssRNA dsDNA -ssRNA Transmission Fecal-oral Blood transfusion, Vertical Blood transfusion, Chronic hepatitis — + Hepatoma Vaccine

sectionⅠ Hepatitis A virus ( HAV ) ⅠBiological properties 1.spherical, 27nm, icosahedral, non-enveloped, VP1-VP4. 2.One serotype. 3.+ssRNA, 7500bp.

ⅠBiological properties 4.Chimpanzee and marmoset are susceptible. 5.Culture: difficult, no CPE, grow slowly.IFA. 6.Resistance: strong, resistant to acid;liposoluble agents, dry, inactivated at 100℃ 5min.

Hepatitis A virus particles found in fecal extracts by immunoelectron microscopy.

Ⅱ.Pathogenesis and immunity 1.Source of infection: patients, subclinical infected person. 2.Transmission: fecal-oral route. 3.Pathogenic mechanism: HAV----mouth----intestine----blood----liver Mechanism of hepatocyte damage: viral direct effect immune injure 4.Immunity: anti-HAV IgG are protective, can neutralize viral infectivity.

Clinical findings: Incubation period:10-50days(30days) acute hepatitis A, rarely chronic Some infected people are asymptomatic Rarely fatal

Ⅲ.Microbiological detection 1.Detect HAV virion, antigen or RNA in feces: IEM, ELISA or RT-PCR. 2.Detect anti-HAV IgM in serum: ELISA. Ⅳ.Control 1.γ-globulin for urgent prevention. 2.Vaccine: attenuated or inactivated vaccines are commonly used. Ⅴ.treatment No special treatment is need because Hepatitis A is self-limiting disease. Supportive care.

SectionⅡ Hepatitis B virus ( HBV ) belong to Hepadnaviridae Ⅰ.Biological properties 1.structure: Partly dsDNA, circular, 3200bp, the long strand(negative strand) is complete, there is a gap in the short strand(positive strand). 2 layer capsids: the inner capsid: icosahedral, carry HBcAg, HBeAg the outer capsid: carry HBsAg, pre-S1 Ag, pre-S2 Ag.

2. 3 different particles can be seen in the blood in HBV infection 1)Dane particle: intact, mature, and infectious virion, 42nm. 2)Small spherical particle: 22nm, carry HBsAg. 3)Tubular particle: 22nm in diameter, 100-700nm in length, mainly consists of HBsAg.

大球形颗粒模式图

3.Gene and encoded proteins 4.ORF: S, C, P, X regions, located in the long strand. S region: HBsAg, pre-S1 protein, pre-S2 protein. C region: HBcAg, HBeAg. P region: DNA polymerase. X region: X protein.

4.Replication There are some parallels between the hepadnaviruses and the retroviruses, in that: 1)Both synthesize DNA from an RNA template 2)There is base sequence homology between the enzymes involved.

5.Ags & Abs 1)HBsAg: 4 subtypes: adr, adw, ayr, ayw; HBsAg ( + ): indicates that the patient is infected with HBV, either as a recent acute infection or as a carrier; anti-HBs: protective.

2) HBcAg: not easily detective in serum anti-HBc: not protective anti-HBc ( + ): viral multiplication, active infection. 3) HBeAg: is correlated strongly with the detection of viral DNA, virions and viral DNA polymerase in the serum; variable. HBeAg ( + ): viral multiplication, active infection. anti-HBe: protective

4)pre-S1 Ag, pre-S2 Ag: be related to the adsorption of virus; enhance the antigenicity of S protein. 6.Can not grow in any cell culture. 7.Chimpanzee is susceptible to HBV. 8.Resistance:low temperature, dry, UV, alcohol, stable 60℃1h, 100℃10min. Sensitive to autoclaving, sodium hypochlorite

Ⅱ.Pathogenesis & immunity 1.Source of infection: patients, HBsAg-carrier. 2.Transmission way: ① By blood or blood products; ② Sexual transmission; ③ Vertical transmission: from mother to child. ④ close contact 3.Mechanism of pathogenesis: hepersensitivity reactions ( type Ⅱ, Ⅲ,Ⅳ ).

Clinical Findings Clinical types: acute, chronic, severe hepatitis, hepatocirrhosis, chronic carrier Carcinogenesis: hepatocellular carcinoma

Carcinogenesis The evidence Hepatoma incidence in hepatitis B patients is higher than that in non- hepatitis B patients. The possibility of detection of HBV infection in hepatoma patients is higher than that of normal people. Integrated HBV DNA (X region) can be found in hepatocyte nucleus of hepatoma. Animal hepatitis viruses can induce hepatoma in animals, and integrated viral DNA can also be found in hepatocyte nucleus.

Ⅲ.Microbiological detection Detecte Ags & Abs: HBsAg, anti-HBs, anti-HBc, HBeAg, anti-Hbe.

Applications of antigen-antibody detection Screen blood donor Help diagnose hepatitis B Help judge the prognosis and outcome Investigate epidemiology of hepatitis B and detect chronic carriers or asymptomatic carriers. Judge people’s immunity level and effect of vaccination.

Interpretation of antigen and antibody HBsAg the presence of HBV infection anti-HBs previous HBV vaccination or previous infection which has recovered the individual obtains protection against re-infection.

Interpretation of antigen and antibody HBeAg the multiplication of HBV virion the patient serum is highly infectious Persistent high titer indicates chronic conversion anti-HBe patient is recovering and get some immunity to HBV

Interpretation of antigen and antibody anti-HBc IgM acute hepatitis B or a recent HBV infection in which replication of virion presents anti-HBc IgG previous HBV infection or chronic HBV infection

Prevention and Treatment Cutting transmission way Treatment Supportive care: major

CONTROL Passive immunization Active immunization Hyperimmune hepatitis B immunoglobulin HBIG Active immunization Vaccine HBsAg

Hepatitis B can be prevented! If you have never had hepatitis B, you can get 3 shots . . . 3 2 1 . . . and get long lasting protection.

if the mother has Hepatitis B Baby Shots for Hepatitis B if the mother has Hepatitis B Birth 1 - 2 months old + Hepatitis B Vaccine Hepatitis B Vaccine H-BIG 6 months old Hepatitis B Vaccine

Geographic Distribution of Chronic HBV Infection HBsAg Prevalence ³8% - High 2-7% - Intermediate <2% - Low 36

sectionⅢ Hepatitis C virus ( HCV ) Ⅰ.Biological properties 1 +ssRNA, 9.4kb. 2 50nm. 3 lipo-enveloped. 4 Human and chimpanzee are susceptible to HCV. 5 Can not culture. 6 easy variation.

Ⅱ.Pathogenesis 1 Transmission: transmitted mainly by blood and blood products. 2 The disease is usually mild. Chronic infection occurs in 80% of cases. 3 HCV is closely related to cirrhosis, hepatoma.

Ⅲ.Microbiological detection 1 Detect anti-HCV: ELISA. 2 Detect viral RNA: RT-PCR. Ⅳ.Control Neither active nor passive immunization is available.

sectionⅣ Hepatitis D virus ( HDV ) Spherical, 35-37nm. –ssRNA, circle, 1700bp. Outer capsid is HBsAg. One serotype. Defective virus. Human and chimpanzee are susceptible to HDV.

Transmission: same as HBV. Infecious mode: Coinfection and Superinfection Detect HDAg & anti-HDV.

sectionⅤ Hepatitis E virus ( HEV ) Ⅰ.Biological properties 1 Spherical, 27-38nm. 2 +ssRNA, 7.2kb. 3 Not grow in cell culture.

Ⅱ.Pathogenesis 1 Transmission: fecal-oral route. 2 Mainly involve young and adults. 3 Incubation period: average 40 days. 4 Cause acute hepatitis, 4-6 weeks recovery, no chronic. 5 Mortality 1-2%, pregnant woman 10-20%. Ⅲ.Microbiological detection 1 Detect viral Ag in faeces: IEM. 2 Detect anti-HEV IgM in serum: ELISA.