Hepatitis Viruses PDF

Hepatitis viruses Picornaviridae Hepadnaviridae Flaviviridae Hepeviridae  HEPATITIS VIRUSES HAV is a picornavirus with a RNA genome; it is sp...

Hepatitis viruses Picornaviridae Hepadnaviridae Flaviviridae Hepeviridae  HEPATITIS VIRUSES HAV is a picornavirus with a RNA genome; it is spread by the fecal-oral route; it causes acute liver disease and rarely causes fatal disease. HBV is a hepadnavirus with a DNA genome; it is spread parenterally by blood or needles, by sexual contact, and perinatally; it causes chronic hepatitis in 5% to 10% of patients and it is associated with primary hepatocellular carcinoma (HCC). HCV is a flavivirus with an RNA genome; it is spread by the same routes as HBV but is more prone to cause chronic disease. HCV also increases risk for HCC. HDV is a defective virus requiring actively replicating HBV as a “helper virus” and occurs only in patients who have active HBV infection. HBV provides an envelope for HDV RNA and its Hepatitis viruses differ greatly in their structure, antigens. mode of replication, mode of transmission, and HEV is an enteric encapsidated virus with an in the time course and sequelae of the disease RNA genome (Hepeviridae), and its disease they cause resembles HAV.  HEPATITIS VIRUSES Hepatitis viruses are hepatotropic, they bind to hepatocytes (susceptible cells) and they replicate in hepatocytes (permissive cells). They are responsible for hepatitis: a systemic disease with primary inflammation of the liver.  HEPATITIS VIRUSES Viral hepatitis can be: o Acute: self-limiting inflammation characterized by structural and functional restoration (< 6 months) o Chronic: persistent infection associated with structural and functional damages (> 6 months) o Fulminant: massive necrosis of liver parenchyma, arising as rare complication of the acute hepatitis  Hepatitis A virus (HAV) o Belongs to the family Picornaviridae o Genus Hepatovirus o One serotype only o Capsid resistant to acid and other treatments o Humans are the only reservoir host (anthroponosis) Genoma: monopartite, linear ssRNA (+) Icosahedral capsid Nonenveloped viruses, 27 nm  HAV HAV is a food-borne enteric virus that can cause widespread outbreaks Ingestion of HAV spreads easily in a contaminated water or community because most food (raw seafood, infected people are contagious fruit, vegetables) 10-14 days before symptoms occur, and most people have inapparent but productive infections HAV replicates slowly in the liver without producing apparent cytopathic effects. Damage to the liver is mainly due to cell-mediated immune responses and antibody- dependent cellular cytotoxicity (→immunopathology) HAV cannot initiate a chronic infection  HAV Clinical syndromes o Incubation: 15-50 days o Jaundice (icterus) o Nausea o Abdominal pain o Asthenia, fever o Frequent subclinical cases o No chronic hepatitis o 0.1%: fulminant hepatitis o Long lasting protective immunity  Diagnosis, treatment and control of HAV infection Serologic tests: anti-HAV IgM and IgG detection in serum samples Prophylaxis with immune serum globulin given before or early in the incubation period (ideally within 2 weeks after exposure) is 80% to 90% effective in preventing clinical illness. Killed HAV vaccines are recommended for all children after 1 year of age and for adults at high risk for infection, as travelers to endemic regions.  Hepatitis B virus (HBV) o Belongs to the family HepaDNAviridae o Genus: Orthohepadnavirus o Genome: partially dsDNA, circular o Icosaedral capsid composed of HBcAg o Enveloped virus (40 nm) presenting the surface antigen HBsAg Reverse transcriptase and ribonuclease H activity  HBV HBV particles Dane particle (40 nm) spherical particle (20 nm) filamentous particle (50-230 nm) Transmission electron microscopy  HBV HBsAg HBx RNA-pol RNAse H HBcAg HBeAg HBV o Virus attachment to hepatocytes and penetration through an unknown mechanism (endocytosis?) o Uncoating and transportation to the nucleus o Macromolecular synthesis: the partially dsDNA genome is completed; transcription leads to pgRNA and subgenomic mRNAs; translation of mRNAs o pgRNA is encapsidated together with DNA pol-RNA dep and retro-trascription occurs inside the nucleocapsid o The ssDNA is converted into the (partial) dsDNA o Virions are released by endocytosis (endoplasmic reticulum membranes)  HBV pgRNA = pregenomic RNA → ssDNA → dsDNA subgenomic mRNAs → proteins  Transmission of HBV Fetus Newborn (rare) Vertical transmission HBV Parenteral transmission Sexual transmission (through contaminated blood and blood (the most common route in components, transfusion, needle sharing, industrialized countries) acupuncture, ear piercing, or tattooing)  Pathogenesis of HBV infection o HBV is not directly cytolytic. o Symptoms are caused by cell-mediated immunity (CMI) and immune complexes. The major source of infectious virus is blood, but HBV can be found in semen, saliva, milk, vaginal and menstrual secretions, and amniotic fluid.  Pathogenesis of HBV infection Not all people with acute HBV infection have symptoms. The presence of signs and symptoms varies by age. Most children