Hepatitis A and B

Types Hepatitis A Hepatitis B Hepatitis C Hepatitis D (also called delta virus) Cannot replicate without another virus Hepatitis E Usually transmitted in much the same way as hepatitis A Non A-E Hepatitis Viruses History Member of the Picornavirus family Identified in 1973 Given many names before Hepatitis A Virus became the predominant name used infectious hepatitis epidemic hepatitis epidemic jaundice catarrhal jaundice infectious icterus Botkins disease MS-1 hepatitis Host Range Hepatitis A infects hepatocytes (liver cells) Known to infect both humans and non-human primates It is not known whether virus can replicate in intestinal cells or not Hepatitis A Structure Non-enveloped, spherical virus Small capsid (27-32 nm) made of 60 copies of 3 different proteins (VP1, VP2, and VP3) 1 single-stranded (+) linear RNA molecule RNA molecule polyadenylated with 40-80 adenines on 3? end VPg attached to 5? end Genomic Expression and Virus Replication Replicates its genome in the same manner as the other picornaviruses (like the poliovirus) Translation occurs immediately after entry into host cell One long polyprotein created from genome Enzymatic protease 3C cleaves polyprotein into 4 capsid proteins (VP1, VP2, VP3, and VP4) and several other proteins Does not metabolically overwhelm the cell Hepatitis A Infection Generally obtained through fecal-oral contact Typically seen in areas where sanitation is poor Widespread infections have occured in day care centers, where caregivers have come in contact with the infected stool of infants Raw shellfish taken from areas where the water has been contaminated by raw sewage also can cause Hepatitis A infection Hepatitis A can also be transmitted by sexual contact Signs, Symptoms, Diagnosis and Treatment Majority of Adults symptomatic, whereas the majority of children are asymptomatic Symptoms develop 2-6 weeks after infection Nausea and vomiting Diarrhea, especially in children Low-grade fever Loss of appetite Rash Tiredness, fatigue Jaundice - A yellow discoloration of the skin and the whites of the eyes Urine is dark brownish in color, like cola or strong tea. Pain in area of liver Symptoms generally go away in 2 months 15% of people experience symptoms that come and go for 6-9 months Diagnosed usually via serology tests (search for HAV antibodies) Usually no treatment is necessary, but vaccines can be given inactivated (Havrix, Vaqta) along with immunoglobulin injections Hepatitis B Host Range and Structure It infects humans and chimpanzees but there are closely related members of this family that infect other mammals and birds. Infects hepatocytes Member of the Hepadnavirus family Enveloped Virus DNA virus Complete (-) strand, partial (+) strand Uses Reverse Transcriptase to replicate its genome Gene Expression The HBV genome has four genes pol encodes viral DNA-polymerase env encodes envelope protein pre-core encodes pre-core protein (which is processed to viral capsid) X encodes protein X, which may be involved in the activation of host cell genes and the development of cancer Genome Replication Uses Reverse Transcriptase to convert an mRNA transcript into the DNA genome Packages the DNA molecule into capsid Hepatitis B Infection HBV is transmitted by blood and blood products and sexual transmission. It is also transmitted from mother to infant in the perinatal period which is a major mode of transmission in regions where hepatitis B is endemic HBV endemic in parts of Asia Major spread of infection in Western nations is due to drug use and sexual contact Symptoms of Hepatitis B infection are similar to Hepatitis A infection, only develop more slowly Fulminant Hepatitis Fulminant hepatitis is an unusual illness. It is a severe form of acute hepatitis that can be life threatening if not treated right away. The symptoms develop very suddenly. Mental disturbances such as confusion, lethargy, extreme sleepiness or hallucinations (hepatic encephalopathy) Sudden collapse with fatigue Jaundice Swelling of the abdomen Treatments for Hepatitis B Interferon Lamivudine Liver transplant Prophylactic treatment for exposure to hepatitis B virus involves either hepatitis B immune globulin (HBIG), hepatitis B vaccine, or a combination of both. The HBIG dose equals 0.06 mL/kg. Efficacy ranges from 70 to 95 percent for different types of exposure. Virus Evasion to Immune Response HBV "evades" the innate response by simply not inducing it to act Acts as a ?stealth? virus early in the infectious process Mutational inactivation of B-cell and T-cell epitopes occurs in chronic HBV infection HBV employs evasion strategies that target the adaptive immune response HBeAg has been shown to suppress the antibody and T-cell response to HBcAg HBx protein has the potential to inhibit antigen processing and presentation if it is overexpressed in infected cells. The hepatitis B surface antigen (HBsAg) might also suppress immune elimination of infected cells by functioning as a high-dose tolerogen, since extremely high serum HBsAg titers, in the mg per ml range, are often seen with chronically infected patients