Hepatitis Viruses II Flashcards
Hepatitis D Virus
- Hepatitis D Virus genus of the Deltaviridae family
- ( - ) ss RNA circular
Hepatitis D Virus Structure and Replication
- Single stranded RNA virus, circular (-) negative
- Requires the presence of hepatitis B surface antigen (HBsAg) for its transmission and assembly but not transcription
- Transcription method not understood
- Transcription is independent of HBV
- Replicates in the nucleus using host polymerase
- HBsAg surrounds the RNA–protein complex of HDV
- Found in people with acute or chronic hepatitis B virus infection
HDV Clinical Disease
- Simultaneous delta and hepatitis B infection
- Superinfection with chronic hepatitis B.
- Permanent hepatitis common
- Accelerate the pace of chronic HBV infection
- HBV and HDV infection could lead to cirrhosis of liver
HDV Diagnosis
•Antibody to delta, PCR
HDV Treatment and Prevention
•The surface protein of HDV is HBsAg and any measures aimed at limiting the transmission of HBV will prevent HDV transmission
Hepatitis C Virus
- Hepatitis C Virus genus of the Flaviviridae family
- ( + ) ss RNA icosohedral enveleoped
HCV Structure
- l Parenterally transmitted (PT)–non–A, non–B hepatitis virus
- (+) Stranded linear RNA of 10 Kb
- Core antigen encloses RNA
- Envelope E1/E2 surrounds the core
- Nonstructural genes encode HCV protease and polymerase activities
- Inhibitors for HCV protease and polymerase available
HCV Replication
- Replicates in the cytoplasm, multiple receptor
- (+) RNA replicates via (–) RNA intermediate
- (+) RNA is translated into a polyprotein and cleaved into mature proteins by proteases
- Virus assembly in the cytoplasm
- Genetic variability observed in the envelope of the virus
- Eleven major genotypes with different geographic distribution and disease severity
- Genotypes 1-3 are common, with genotype 1a predominating in North America
HCV Incubation
- Incubation period averages 6 - 12 weeks
- Acute phase is mild, asymptomatic in 75%
- Results in chronic disease in more than 85% of patients
HCV Clinical Disease
- Was associated with mainly with blood transfusions until blood screening for HCV was introduced
- Sexually transmitted but to a lesser extent than hepatitis B
- Needle sharing accounts for up to 40% of cases
- Worldwide distribution
- Slow disease progression (average 10 -18 years), chronicity tends to wax and wane
- Could lead to cirrhosis of liver (10-20% with chronic infection) and hepatocellular carcinoma (1-5%).
- Chronic hepatitis C is the leading cause of liver transplantation in the United States
- Mechanism of oncogenicity unclear
- Role of HCV core and non-structural proteins have been implicated
HCV Pathogenesis
- Rate of HCV replication 1X1012 virions per day
- 10% hepatocytes are infected
- Some direct viral cytopathic effect, but hepatocytes are mainly killed by cytotoxic T cells (CTL) – Type IV hypersensitivity
- Proinflammatory cytokines are release by innate immune cells, INF-alpha/beta initially controls viral infection
- Th1 T cells lead to more necrosis and apoptosis
- Chronic HCV infection promotes insulin resistance by increasing inflammatory response, TNF-alpha and IL-6 leading to progression of cirrhosis & HCC
HCV Diagnosis
- Antibody detection by ELISA
- Confirmation by PCR (RT-PCR)
- Elevated liver enzyme alanine amino transferase (ALT)
HCV Treatment First Line
- Interferon-a with ribavirin: first line of treatment, response better in patients with genotypes other than I and lower viral load.
- Virus comes back after sometime
HCV Treatment - Protease Inhibitors
- Telaprevir (Incivek), Boceprevir (Victrelis) and simeprivir (Olysio).
- Develops resistance, works better if combined with interferon + ribavirin. The second generation of protease inhibitors include semeprevir, paritaprevir, and grazoprevir
HCV Treatment - Polymerase Inhibitors
- The nucleotide HCV RNA polymerase inhibitor includes sofosbuvir (Sovaldi) that terminates the RNA synthesis of HCV.
- The nonnucleoside HCV polymerase inhibitor includes dasabuvir that inhibits HCV RNA polymerase.
HCV Treatment - NS5A (phosphoprotein) inhibitors
•The inhibitors of HCV NS5A phosphoprotein, that is critical for HCV replication, includes daclatasvir, elbasvir, ledipasvir, ombitasvir, and velpatasvir.
HCV Treatment - Combination Therapy
•Combination therapy that includes interferon-α and ribavirin, interferon and ribavirin plus a HCV protease inhibitor or a HCV polymerase inhibitor are used that works better for some genotypes than others.
HCV Treatment - New Combination Therapy
•includes non-interferon combination in 7 combinations: 1) a fixed-dose combination of sofosbuvir (HCV polymerase inhibitor)— velpatasvir (NS5A inhibitor) plus ribavirin for genotype 1, 2, 3, 4, 5; 2) dasabuvir (nonnucleoside HCV polymerase inhibitor), ombitasvir (NS5A inhibitor), paritaprevir (HCV protease inhibitor) plus ritonavir (HIV protease inhibitor, increases levels of paritaprevir); and 5 more combinations
Hepatitis E Virus
- Hepatitis E Virus genus of the Hepeviridae family
- ( + ) ss RNA icosohedral naked
- spikes on surface
- Most cases in India and in other countries with poor sanitation
- Rarely identified in the United States
HEV Structure and Replication
- ET non–A, non–B hepatitis virus (enterically transmitted
- RNA virus similar to calicivirus, ss (+) RNA
- Spherical 27 to 34 mm particle
- Unenveloped, spikes on surface
HEV Clinical Disease
- Transmitted through fecal–oral route
- Causes acute disease like HAV
- May fulminate especially in pregnant women
HEV Diagnosis
- Immunological assays
- Presence of specific IgM l Detection of RNA by PCR
HEV Prevention
•Not known if immune serum globulin prevents infection
HEV Treatment
•No treatment is available
