PowerPoint PresentationSlide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Slide 34Slide 35Slide 36Slide 37Slide 38Slide 39Slide 40Slide 41Slide 42Slide 43Slide 44Slide 45Slide 46Slide 47Slide 48Slide 49Slide 50Slide 51Slide 52Slide 53Slide 54Slide 55Slide 56Slide 57Slide 58Lecture 29Hepatitis VirusesLecture 29Hepatitis VirusesHepatitis:Inflammation of the liverCauses: Toxic (alcoholic), Infectious (parasites, fungi, bacterial, viral) and Autoimmune. Self-limited hepatitis: short duration, no carrier stateChronic persistent hepatitis: virus persists without symptomsChronic active hepatitis: virus persists and causes necrosis, fibrosis leading to cirrhosis and liver failure. May have periods without symptoms. Symptoms include jaundice, anorexia, flu-like, vomiting, nausea, colitis and autoimmune disease.Types:Fibrosis: After becoming inflamed, the liver repairs itself and scarring occurs.Cirrhosis: Scars begin to join together, nodules may form, blood flow is blocked. The liver shrinks and becomes hard. Liver failure: Severe cirrhosis, liver is unable to filter wastes, toxins and drugs from the blood. Does not produce clotting factors.Healthy liver Viral hepatitisProgression of Liver Disease4 Functions 1. Purification…………removes drugs/toxins/ alcohol 2. Synthesis…………..protein metabolism, serum proteins, bile, clotting factors 3. Storage……………..mineral, vitamins, sugars 4. Transformation…….converts hormones into active formsLargest internal organLiverA B C D EBloodsexualBloodsexualBloodsexualSource and transmissionfecal-oralChronicinfectionno yes yes yes noPrevention immunization immunization blood donorscreening;risk behaviormodificationimmunization;risk behaviormodificationensure safedrinkingwaterType of HepatitisViral Hepatitis – Overviewfecal-oralrisk behaviormodificationHepatitis A VirusHepatitis A VirusSmall RNA virusNon-enveloped Picornavirus family Pico (greek very small) RNA virus (Polio, Rhinovirus)Single serotypeAcute or asymptomaticProtective antibody confers lifelong immunityAcid stableAcquired from contaminated water, shellfish, salad22,700 cases in US per year, <0.4% cases are fatalHAV OverviewChildren <6 years of age usually are asymptomatic (70%) Usually (30%) anicteric (no jaundice) After an incubation period of 28 days……nonspecific illness fever, malaise, anorexia, Followed by gastrointestinal symptoms…nausea, abdominal discomfort, dark urine and jaundice (70-80%) Course of illness usually <2 months 15-20% of patients relapse lasting up to 6 months Acute liver failure is rare (0.015-0.5%)….usually young children and older adultsSymptoms of HAVCONCENTRATION OF HEPATITIS A VIRUSIN VARIOUS BODY FLUIDS GEOGRAPHIC DISTRIBUTION OF HEPATITIS A VIRUS INFECTIONGenomic RNA is infectious (1 million times less infectious than particles)Hepatitis A particles consist of one RNA molecule surrounded by capsid proteinsThe structural and non-structural proteins and the highly structured 5´ and 3´ UTRs are represented. The HAV GenomeCapsid proteinsVPgproteasepolymeraseHAV Life CycleThe HAV life cycle. (a) The virus enters the hepatocyte via an interaction with a cellular receptor. (b) This is followed by uncoating of the viral particle and release of the positive-sense RNA genome into the cell. (c) An internal ribosome entry site within the 5 nontranslated segment of the genome mediates cap-independent translation of the viral polyprotein. (d) The polyprotein undergoes co- and post-translational proteolytic processing directed by the viral protease, 3C. (e) Nonstructural viral proteins assemble and commence synthesis of a negative-strand copy of the viral genome. (f) The negative-strand copy of the genome is used as template for synthesis of multiple new copies of genomic positive-strand RNA. (g) Some of this newly synthesized positive-sense RNA is recycled for further RNA synthesis or translation. (h) Other positive-strand RNA molecules are packaged into new viral particles formed by assembly of the structural proteins. (i) Newly assembled HAV particles are secreted by the cell across the apical membrane of the hepatocyte into the bile duct, from which they are passed into the bile and small intestine.HAV Life CycleTreatment 99% of patients recover without treatment. Rest and proper nutrition results in recovery at 2 months.Vaccine Cell culture-adapted virus grown in human fibroblasts. Purified product inactivated with formalin. HAV: Treatment and VaccineHepatitis B VirusHepatitis B Virus350 million chronic carriers in the world (250 million in Asia Pacific)In U.S. 1.2 million carriers, 5,500 deaths per yearHBV OverviewEnveloped virus Double-stranded DNA virusFamily: Hepadnaviridae Hepa*DNA*virusEight genotypes of HBV, designated genotypes a-hChronic liver disease……………………….10% → 25% cirrhosis + liver cancerAcute case fatality rate………………………1%Acute, recovery with immunity…………….90%One third of world population has been infected with HBVOne third of patients have “silent” diseaseSymptoms include: fever, headache, muscle aches, fatigue, loss of appetite, nausea, vomiting and diarrhea, dark urine, abdominal pain, jaundice.Symptoms of HBVHepatitis B Virus Particles3.2 Kb DNA3.2 Kb DNApolymerasepolymeraseCore Core SurfaceSurface1. Replication occurs in the nucleus2. Genomic integration can occur3. Reverse transcriptase (RNA to