1 / 30

Hepatitis Viruses

Hepatitis Viruses. Fe A. Bartolome, MD Department of Microbiology Our Lady of Fatima University. HEPATITIS A. infectious hepatitis; Enterovirus 72 Picornavirus genus Heparnavirus/Hepatovirus naked, icosahedral symmetry positive sense, ssRNA virus with a VPg protein attached to 5” end

rivka
Download Presentation

Hepatitis Viruses

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Hepatitis Viruses Fe A. Bartolome, MD Department of Microbiology Our Lady of Fatima University

  2. HEPATITIS A • infectious hepatitis; Enterovirus 72 • Picornavirus genus Heparnavirus/Hepatovirus • naked, icosahedral symmetry • positive sense, ssRNA virus • with a VPg protein attached to 5” end • replication similar to other Picornaviruses • not cytolytic • released by exocytosis

  3. HEPATITIS A • Characteristics: • Stable to: acid (pH 1), solvents (ether, chloroform), detergents, salt/ground water, drying, temperature (40C – 560C) • Inactivated by: chlorine treatment, formalin, UV radiation

  4. HEPATITIS A • Pathogenesis: • MOT: fecal-oral  food (shellfish – clams, oysters, mussels); water; dirty hands • Ingestion  oropharynx or epithelial lining of intestines  blood stream  liver (hepatocytes and Kupffer cells)  bile  stool • Virus shedding: 2-3 wks before & 1 week after onset of jaundice or until antibody is detected • Interferon – limits viral shedding • NK cells & cytotoxic T cells  lysis of infected cells • Antibody, complement, ADCC  induce immunopathology

  5. HEPATITIS A • Pathogenesis: • MOT: fecal-oral  food (shellfish – clams, oysters, mussels); water; dirty hands • Ingestion  oropharynx or epithelial lining of intestines  blood stream  liver (hepatocytes and Kupffer cells)  bile  stool • Virus shedding: 2-3 wks before & 1 week after onset of jaundice or until antibody is detected • Interferon – limits viral shedding • NK cells & cytotoxic T cells  lysis of infected cells • Antibody, complement, ADCC  induce immunopathology

  6. HEPATITIS A • Epidemiology: • 90% of infected children & 20-25% of infected adults with inapparent but productive infections • HAV viremia transient  blood-borne transmission rare

  7. HEPATITIS A • Clinical Syndromes: • Children: mild infection, usually asymptomatic • Adults: abrupt onset of symptoms • viral shedding precedes onset of symptoms • complete recovery in 99% • fulminant hepatitis: 1-3 persons/1000 with 80% mortality • immune complex-related symptoms rare

  8. HEPATITIS A • Laboratory Diagnosis: • ELISA or radioimmunoassay • (+) IgM anti-HAV  acute infection  fecal shedding decreases as IgM titer increases • (+) IgG anti-HAV  resolution, past infection • Prophylaxis: immune serum globulin < 2 wks after exposure

  9. HEPATITIS B • serum hepatitis • Hepadnavirus • infects liver, kidneys and pancreas  humans and chimpanzees • 15% of population infected during birth or childhood • small, enveloped • circular, partly ds DNA virus • mature virion  Dane particle

  10. HEPATITIS B • Important proteins: • DNA polymerase – with reverse transcriptase & ribonuclease H activity • HBcAg – core antigen; surrounds polymerase; T cell antigens • HBeAg – minor component of virion; primarily secreted into serum • HBsAg – surface antigen; Australia antigen • HBx – transcriptional transactivator; promote viral replication; protein kinase

  11. HEPATITIS B • HBsAg with 3 glycoproteins encoded by same gene but translated from different AUG start codons • S (gp27) – contained in M glycoprotein; major component of HBsAg • M (gp36) – contained in the L glycoprotein • L (gp42) – essential for virion assembly

  12. HEPATITIS B • Replication unique: • With distinctly defined tropism for liver • Small genome  economy in transcription and translation • Replicates through an RNA intermediate • Binds to human serum albumin  target the virus to the liver • Cell penetration  partial DNA strand converted to complete dsDNA  nucleus

  13. HEPATITIS B • two phases of hepatocyte infection: • Proliferative phase • HBV DNA present in episomal form • Viral HBsAg & HBcAg + MHC class I molecules  activation of CD8+ T cells  (+) hepatocyte destruction • Integrative phase • For hepatocytes not destroyed by immune system  viral DNA incorporated into host genome

  14. HEPATITIS B • (+) HBsAg and HBeAg in blood  on-going active infection • MOT: • Blood & other body fluids – semen, saliva, milk, vaginal secretions, amniotic fluid • Sexual contact • Perinatal – passage through birth canal • Intracellular accumulation of filamentous forms of HBsAg  responsible for characteristic ground glass cytopathology

  15. HEPATITIS B • CMI + inflammation  responsible for causing symptoms; eliminate infected hepatocytes • Immune complexes between HBsAg and anti-HBs  (+) type III HS reaction  vasculitis, arthralgia, rash, renal damage • Infants & young children  immarture CMI  less ability to resolve infection  90% chronic carriers

  16. Ab Immune complex Type III HS HBsAg Symptoms, resolution Liver Viremia CMI Ab Prevent spread & disease MOT Blood HEPATITIS B • Spread of Hepatitis B

  17. Acute Hepatitis B 90% 1% 9% Resolution Fulminant HBsAg+ > 6 months 50% Asymptomatic carrier state Chronic persistent hepatitis Chronic active hepatitis Resolution Extrahepatic disease: PAN, GN HCC Cirrhosis HEPATITIS B • Clinical outcomes:

  18. HEPATITIS B • Laboratory: • Detection of HBeAg is the best correlate to the presence of infectious virus • Chronic infection  continued finding of HBeAg, HBsAg or both without detectable antibodies

  19. HEPATITIS B Interpretation of Serologic Markers of HBV Infection

  20. HEPATITIS C • NANB post-transfusion hepatitis • Flavivirus genus Hepacivirus • Enveloped, ss positive sense RNA virus • 5’ end encodes nucleocapsid core protein  highly conserved • Envelope proteins  E1 and E2 • Hypervariable regions (HVR1 & 2)  present in E2 sequence • Non-structural proteins (e.g. NS5B  viral RNA-dependent RNA polymerase)  with poor fidelity

  21. HEPATITIS C • Infects only humans and chimpanzees • Binds to cells with CD81 surface receptors OR coats itself with LDL or VLDL & uses their receptors for uptake into hepatocytes • Inhibit apoptosis & IFN- by binding to TNFR and protein kinase R (PKR)  prevent death of host cell and promote persistent infection • CMI  production of tissue damage • Antibody not protective

  22. HEPATITIS C • Remains cell-associated • MOT: • Parenteral - >90% of HIV (+) individuals infected with HCV • Secretions • Sexual • Perinatal (6%) • PERSISTENT INFECTION AND CHRONIC HEPATITIS ARE THE HALLMARKS!

  23. HCV Acute infection Recovery & clearance Persistent infection Chronic hepatitis Liver failure Cirrhosis HCC HEPATITIS C • Outcomes:

  24. HEPATITIS C • Laboratory: • (+) anti-HCV antibodies (50-70%) in symptomatic acute infection • HCV RNA persists despite presence of neutralizing antibodies (90%) • Episodic elevation of serum aminotransferases • Treatment: IFN- alone or with ribavirin – only known treatment

  25. HEPATITIS D • Delta hepatitis; viroid-like • Replication defective  viral parasite • Enveloped, circular RNA virus  surrounded by delta antigen core  surrounded by HBsAg-containing envelope • Unusual transcription and replication process • Host cell RNA pol II  makes RNA copy  replicates genome  makes mRNA  form a ribozyme  cleave RNA circle  form mRNA

  26. HEPATITIS D • MOT similar to HBV • Replicate and cause disease only in people with active HBV infection  results in cytotoxicity and liver damage • With direct cytopathic effect

  27. HEPATITIS D • Clinical outcomes: Co-infection HDV + HBV Healthy individual rare 3-4% 90% Recovery w/ immunity Chronic HBV/HDV hepatitis Fulminant hepatitis Death Cirrhosis

  28. HDV HBV carrier 80% 7-10% 10-15% Acute, severe disease Chronic HBV/HDV hepatitis Fulminant hepatitis Death Recovery Cirrhosis HEPATITIS D • Clinical outcomes: Superinfection

  29. HEPATITIS E • Enteric or epidemic NANB hepatitis • MOT: fecal-oral • Resembles Calicivirus or Norwalk agent in size and structure  non-enveloped, ssRNA virus • Symptoms and course similar to HAV • Causes only acute disease • Poor response to serum IgG • Infection serious in pregnant women  mortality approx. 20%

  30. HEPATITIS G • Flavivirus similar to HCV • MOT: contaminated blood or blood products; possibly sexual • In 75% of infection  HGV cleared from plasma; 25% become chronic • Site of replication: mononuclear cells  not hepatotropic • Does not cause elevation in serum aminotransferases • With protective effect on patients co-infected with HIV  inhibit HIV replication in cultures of peripheral blood mononuclear cells

More Related