医学微生物学英文版教学课件：第26章HBV-HAV

1、Hepatitis VirusesChapter 26itemHAVHBVHCVHDVHEVClassific-ationPicornavirusesHepadnavirusesFlavi-virusesDefective virusCalicivirusesDiameter(nm)274236-623632Nucleic acid+ssRNAdsDNA+ssRNA-ssRNA+ssRNAType of Hepatitis Source ofvirusfecesblood/blood-derivedbody fluidsblood/blood-derivedbody fluidsblood/b

2、lood-derivedbody fluidsfecesRoute oftransmissionfecal-oralBlood transfusion,VerticalBloodtransfusion,Verticalfecal-oralChronicInfectionCarcinomaNoNoYesYesYesYesYes-NoNoPrevention Abimmunization Abimmunizationblood donorscreening;risk behaviormodification Abrisk behaviormodificationensure safedrinkin

3、gwater Type of HepatitisABCDEBloodtransfusion,VerticalViral Hepatitis - Historical PerspectivesInfectiousViral hepatitisSerumEntericallytransmittedParenterallytransmittedF, G, TTV? otherBDAECNANBSection 1Hepatitis A virus Hepatitis A virus ( HAV )A picornavirus, now classified as a hepatovirus, form

4、erly known as enterovirus 72 .Biological properties1.spherical, 27nm. 2.+ssRNA, 7500bp, which codes for 4 proteins ; capsid: icosahedral symmetry3.one serotype 4.replicative cycle similar to that of other enterovirus 5. Resistance: resistant to pH 210，organicsolvent 60 1h; 100 5min. UV, 1 minute , f

5、ormalin (1:4000 ) , at 37 3 days, chlorine (1015 ppm ), 30 minutes.6.Culture: Vero, humanembryonickidneycells grow slowly, no CPE susceptible animals：chimpanzee and marmoset1.Source of infection: patients, subclinical infected person.2.Transmission: fecal-oral route blood exposure (rare) HAVmouth in

6、testine blood liver3. Immunopathologicinjury Pathogenesis and Immunity an incubation period of 15 to 45 days (mean, 30 days) fever; anorexia (poor appetite); nausea; pain in the right upper abdominal; dark urine and clay-colored stools. jaundicechronic infection is rarealmost all cases (99%) of hepa

7、titis A are self-limiting.Hepatitis A - Clinical Features An epidemic of HAV that occurred in Shanghai, China, in 1988 in which 300,000 people were infected with the virus resulted from eating clams obtained from a polluted river.3.Immunity: anti-HAV IgG are protective, can neutralize viral infectiv

8、ity.Microbiological detection Serological detection detect HAV antigen detect anti-HAV Ab: acute infection is diagnosed by the detection of HAV-IgM Ab in serum detection of HAV-IgA Ab in feces past Infection is diagnosed by the detection of HAV-IgG Ab. Nucleic acid detection RT-PCRControl 1. cut off

9、transmission routes 2.-globulin for urgent prevention. 3.Vaccine: inactivated vaccines attenuated-live vaccineSection 2 Hepatitis B virus Biological propertiesMorphology and structureMorphology Spherical, 42nm three different particles in patients serum 1)Dane particle: intact virion, 42nm. 2)Small

10、spherical particle: 22nm, carry HBsAg. 3)Tubular particle: long filaments 22nm wide, consists of HBsAg.2. Structure core: a partially double-stranded circular DNA 3200bp; the long strand is complete, variable length of the short strand(50-80%). DNA-dependent DNA polymerase capsid: icosahedral symmet

11、ry HBcAg envelope: HBsAg, pre-S Ag. 包膜 S region: HBsAg, pre-S1 Ag, pre-S2 Ag. C region: HBcAg, HBeAg. P region: DNA polymerase. X region: X protein. Gene and encoded proteins4 ORF: S, C, P, X regions, located in the long strand. S region:Envelope protein-HBsAg S protein226aaM protein281aaL protein38

12、9aa53 Pre-S1 Pre-S2 SATGATGATGHBsAg ( + ): indicate that the patient is infected with HBV, either as a recent acute infection or as a carrier; anti-HBs: protective.HBsAg: 4 subtypes: adr, adw, ayr, ayw; adw predominates in Europe,America and Australia adr predominates in China and Japan the 122th am

13、ino acidlysine(d)arginine(y)lysine(w)arginine(r)aadwaywadrayrHBsAg subtypethe 160th amino acid preS1 Ag and preS2 Ag: * be related to the adsorption of virus;* enhance the antigenicity of S protein. anti-preS1: protective, neutralizing Ab anti-preS2: protective, neutralizing AbC region: HBcAg and HB

14、eAg Pre-c CAUGAUG183aaHBcAgEndoplasmic reticulum signal peptide enzyme19aaP25e P23e Golgi proteaseNCP20e P18e P16e HBeAg HBcAg-capsid protein HBeAg-secretedout of thecell HBc Ag*Exist in: the Dane paticle ; the surface of the virusinfected liver cells *Difficult to detect in the blood*anti-HBc (IgG、

15、IgM); not protective anti-HBc (+) : indicate that the virus replication, infectious.* Stimulate CTL response , play an important role in eliminate HBV from host. HBeAg*Exist in: the blood and the surface of the virusinfected liver cells*HBeAg(+): indicate that the virus replication, and havestronger

16、infectivity*anti-HBe: viral multiplication and active infection are reduced, has less infectious, favourableprognosis.DNA polymeraseP region:TPspacerDNApol/RTRnase H *P gene-3.5kb mRNA- pregenome -DNA *Polymerase protein that contain several functions: DNA polymerase reverse transcriptase Rnase HX r

17、egion: X protein transcriptional transactivator associated with the development of liver cancer Replication Unique replication using a reverse transcriptase step 3.5kb mRNA: full-length mRNA; pregenome RNA coding C protein, P protein transcription of viral gene2.4kb mRNA:coding pre-S1 protein 2.1kb

18、mRNA:coding pre-S2 protein, S protein0.7kb mRNA: coding X proteinvariation1.pre-S/S gene: S145 G A, GGA AGA ， lose of antigen site S126C G/A, ACT AGT /AAT, immuneescape 2.pre-C/C gene: C23 G A, TGG TAG, reduce the generation of HBe protein C 18410 1 (CTL epitopes): immuneescape3. P gene: point mutat

19、ion # pregenome cannot be packaged into capsid # produce drug-resistant strain culture chimpanzee , marmoset cannot grow in any cell culture.Resistance stable : dry, UV , 75% alcohol inactivation: 100 10 min. 0.5% peracetic Acid ethylene oxide 5%sodium hypochlorite Pathogenesis and immunity1.Source

20、of infection: patients, HBV-carrier.2.Transmission way: blood or blood products; sexual transmission; vertical transmission: from mother to child.3.Mechanism of pathogenesis: hypersensitivity reactions ( type , , )The viral antigen (HBsAg)-on the surface of the cells Ab, complement; CTL autologous a

21、ntigen-LSPAg-Ab complexes- vasculitis, arthralgia, glomerulonephritis. Variation HBV preC mutate-HbeAg -immunal escape Diseases1. Active Hepatitis - symptomatic 2.Chronic persistent hepatitis asymptomatic Chronic Active Hepatitis - symptomatic exacerbations of hepatitis3. Cirrhosis of Liver4. Hepato

22、cellular CarcinomaMicrobiological detection1. Detecte Ags & Abs: HBsAg, anti-HBs, anti-HBc, HBeAg, anti-HBe.HBsAg - used as a general marker of infection: patients, HBV-carrierHBsAb - used to document recovery and/or immunity to HBV infection. anti-HBc IgM - marker of acute infection.anti-HBc IgG -

23、past or chronic infection.HBeAg - indicates active replication of virus and therefore infectiveness.Anti-HBe - viral multiplication and active infection are reduced, has less infectious2. HBV DNA HBV-DNA - indicates active replication of virus, more accurate than HBeAg especially in cases of escape

24、mutants. Used mainly for monitoring response to therapy.3. Sera DNA polymerase Prevention & treatment1.Control Vaccination-highly effective recombinant vaccines are now available. vaccine can be given to those who are : 1) neonatus 2) health care workers 3) infants of HBV carrier mothersHepatitis B

25、Immunoglobulin - HBIg may be used to protect persons who are exposed to hepatitis B. efficacious within 48 hours of the incident. # the wound contaminated HBV infected blood #sexual partners of chronic carriers # neonatus of HBV carrier mothersOther measures - screening of blood donors - prevent iat

26、rogenic transmission 2.TreatmentInterferonIFN for HBeAg(+) carriers with chronic active hepatitis. Response rate is 30 to 40%.Lamivudine-inhibit DNA polymerase Chinese herbs Successful response to treatment will result in the disappearance of HBsAg, HBV-DNA, and seroconversion to HBeAg.Section 3 Hep

27、atitis C virus 1. spherical, 50nm core: +ssRNA ,9.5kb capsid: C Ag；icosahedral symmetry envelope：E1 E2 Biological properties 2. Antigenicity: E1, E2 -easy variation neutralizingantibody C22- induce cellular immune response C33- variation ；anti-C33c Ab 3. difficult to cultivate 4.resistance： weaklyPa

28、thogenesis and immunity1.transmission: transmitted mainly by blood and blood products.2. easily become chronic infection closely related to hepatoma3. cytocidal effect cell apoptosisimmunopathological injury4. Ag variation immuneescape Microbiological detection: detect viral RNA detect anti-HCV Ab d

29、etect HCV AgPrevention and treatment 1. neither active nor passive immunization is available. 2. screening of blood donors 3.IFN; ribavirin; DAASection 4Hepatitis D virus1. spherical, 35-37nm. 2. core: ssRNA, circle, 1.7kb capsid: icosahedral symmetry HDAg ( Ag) envelope: HBsAg3. defective virus-RNAHD AgHBS Ag4. Human and chimpanzee are susceptible