Viral Hepatitis (Microbiology) PDF

Viral Hepatitis (Microbiology) Beatrice Saviola, Ph.D. Conflict of interest Disclosure In relation to this presentation, Dr. Saviola has no financial interests or other conflicts that need to be discloses. 2  Medi...

Viral Hepatitis (Microbiology) Beatrice Saviola, Ph.D. Conflict of interest Disclosure In relation to this presentation, Dr. Saviola has no financial interests or other conflicts that need to be discloses. 2  Medical Microbiology & Immunology Warren Levinson Chapter 41- Hepatitis Viruses https://accessmedicine-mhmedical- com.proxy.westernu.edu/book.aspx?bookid=3123#261979831  Objectives The student will be able to: Describe the major viral structural characteristics, replication processes, pathogenic processes, and disease processes of HAV, HBV, HCV, HDV, HEV. Families of DNA Viruses HBV  Hepadnaviridae (Hepa-liver and DNA) Icosahedral enveloped virus Unique DNA structure (nicked partially double stranded circular DNA). The viral enzyme for DNA synthesis is reverse transcriptase. It replicates using RNA intermediate. Hepatitis B virus (HBV)-causes serum hepatitis or long-incubation hepatitis. Transmission may be sexual or perinatal or other close contact. In the U.S. blood is an important means of transmission, as is needle sharing, drug straws, and needle sticks by health care workers. Vaccine available. Life cycle of HBV within hepatocyte- Reverse Transcriptase  Enveloped viruses are typically released by budding from the host cell. Enveloped viruses are more susceptible to disinfection (do not persist outside the body or on surfaces long periods of time. Several antigens produced including: HBcAg-core antigen (capsid antigen). Is detectable during an acute or chronic infection. HBeAg-breakdown product of core antigen. Is detectable during an acute or chronic infection. HBsAg-surface antigen (the neutralizing antigen and basis for the subunit vaccine), This antigen is released into the blood and can serve as a decoy particle. Decoy particles may act to interfere with the host’s immune system. Is detectable during an active acute or chronic infection, though in some low-level chronic infections it may not be detectable. Antibodies generated can denote patterns of infection such as acute or chronic infection, or immunity due to previous infection or vaccination. Hepadnavirus with HbsAgs decoy particles that are released into serum of infected people  CD8 + T-cells target infected hepatocytes and target them for destruction, helps clear acute infection/acute hepatitis. HBV can lead to chronic infection, chronic hepatitis, and liver damage due to CD 8 + T-cells immune action. Continued viral replication and liver damage can lead to hepatocellular carcinoma. Worldwide prevalence of hepatitis B carriers and primary hepatocellular carcinoma  Symptoms- abdominal pain, dark urine, pale stool, fever, nausea, weakness, yellowing of eyes and skin, loss of appetite. 2-6 % of adults develop a chronic infection, 90% of infants infected develop a chronic infection. Vaccine available to generate immunity (subunit vaccine based on HBsAg), immunoglobin available to prevent infection upon exposure (in conjunction with vaccine), and a variety of antiviral drugs available to treat chronic infections, Some chronic infections require a liver transplant. HDV  Unclassified RNA Viruses Hepatitis D (HDV, delta agent, or deltaviridae) causes Hepatitis D or delta hepatitis. Hepatitis D is a DEFECTIVE virus and can only replicate with the aid of HBV virus. REQUIRES HBV surface antigen to be a complete virus. Found in the late 70’s in hepatocytes in some Hepatitis B patients. Its envelope protein is HBsAg (comes from HBV). Its nucleic acid is tiny circular –SSRNA (negative sense) with no homology to Hepatitis B DNA, icosahedral capsid. HDV Replication  2 Patterns HDV Infection Infects with HBV (at same time) as a coinfection. Or superinfects- previous infection HBV chronic infection and HDV infects later likely resulting in a chronic HDV infection (this results in worse symptoms). Possibly associated with hepatocellular carcinoma. Transmitted via same routes as HBV- sexual, blood, perinatal. HAV Positive-sense single-stranded RNA virus- RNA alone is infectious. It acts as messenger RNA Picornaviridae (small RNA viruses) Naked icosahedral nucleocapsid, usually cytolytic infections. Subfamilies: viruses causing infection in man: Enteroviruses: acid-stable, resistant to harsh environmental conditions, transmitted by fecal-oral route. Rhinovirus- common cold HAV- acute hepatitis, transmitted by fecal- oral route. Pathogenesis of picornavirus infection Hepatitis A Virus- (infectious hepatitis, short incubation hepatitis) Hepatitis A transmitted by a fecal-oral route, resistant to disinfection and acid. Causes ACUTE hepatitis. Symptoms- Fatigue, nausea, abdominal pain, dark urine, pale stool, fever, yellow eyes and skin. HAV Outbreak in San Diego in 2023 HEV Hepeviridae-calicivirus like (+ssRNA) Hepatitis E virus- fairly similar to the caliciviruses, also unenveloped. It causes epidemic outbreaks of acute hepatitis in parts of the world with poor sanitation. It is spread by a fecal-oral route of transmission. (also eating undercooked pork or venison). It depends on the strain HEV-1 to HEV-4 and HEV-7 as to pattern of transmission. Acute hepatitis. Infection is frequently subclinical but when symptomatic it causes acute disease. It can be fatal in populations such as pregnant women.  Replication of HEV-goes through a quasi enveloped stage, RNA pol, does not bring enzyme within virion.  Symptoms- Fatigue, nausea, abdominal pain, dark urine, pale stool, fever, yellow eyes and skin. Hepatitis E worldwide distribution  Hepatitis E caused primarly by HEV-1 and HEV-2 worldwide transmitted via a fecal-oral route, with HEV-3 predominantly in the US which is transmitted via undercooked meat and animals (zoonotic) HCV  HCV- a flavivirus Flavivirus family contain subfamilies and viruses: Arboviruses (many viruses)- arthropod borne viruses like zika and West Nile virus. And HCV is a separate member of this family- not an arbovirus. +ssRNA viruses, icosahedral, enveloped Susceptible to disinfection.  Hepatitis C virus (HCV) It causes acute (15-45% of cases) and chronic hepatitis (55-85% of cases). Chronic cases may be asymptomatic for 10 to 30 years, but result in cirrhosis, liver failure, or hepatocellular carcinoma. Exposure to infected blood via IV drug use is the most common means of transmission, needle stick, and blood transmission. The virus is also sexually transmitted, or perinatally.  Symptoms- fatigue, fever, nausea, abdominal pain, dark urine, pale stool, yellow eyes. Or often no symptoms. Drug straws can transmit HCV  In chronic HCV infection cytotoxic T-cells (CD8 T Cell) target infected cells, cause hepatocyte damage. Continued damage can lead to hepatocellular carcinoma. No vaccine. Antivirals are available to treat the infection in a course as short as 8-12 weeks, very expensive if insurance will not cover the treatment.  Summary HAV-Fecal-oral**, acute, resistant to disinfection, naked icosahedral +ssRNA. HBV-Bloodborne, sexual, perinatal, icosahedral enveloped, susceptible to disinfection, acute and chronic hepatitis, hepatocellular carcinoma, CD8 + T-cell damage, reverse transcriptase, decoy particles, partial ds DNA. HCV-Bloodborne, sexual, perinatal, enveloped icosahedral +ssRNA, susceptible to disinfection, acute and chronic hepatitis, hepatocellular carcinoma, CD8 + T-cell damage. HDV-Defective virus depends on HBV, Bloodborne, sexual, perinatal, icosahedral enveloped-ssRNA, susceptible to disinfection, chronic hepatitis, hepatocellular carcinoma, CD8 + T-cell damage. HEV- Fecal-oral**, naked icosahedral +ssRNA, resistant to disinfection, acute, developing countries, pregnant women.