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Hepatitis B & C Viruses Mohammadreza Haghshenas PhD of Virology, Faculty of Medicine, Mazandaran University of Medical Sciences Sari, Iran

Viral Hepatitis - Historical Perspectives Enterically transmitted “Infectious” A E Viral hepatitis NANB Parenterally transmitted “Serum” B D C F, G, TTV ? other 2

HBV & HCV are viruses that infect liver and cause liver cirrhosis and liver cancer

Hepatitis B Virus Hepatitis B is a serious disease caused by a virus that infects the liver

Silent Killer 1 out of 3 people have been infected. Most people with HBV do not have any symptoms until it is too late 1 in 4 adults with chronic HBV will die from liver cancer or liver cirrhosis (WHO) An estimated 1 million people die each year from hepatitis B and its complications.

HBV Transmission Parenteral - IV drug abusers, health workers are at increased risk. Sexual - sex workers and homosexuals are particular at risk. Perinatal (Vertical) – mother (HBeAg+) →infant. 2 2 2

Hepatitis B Virus - Virology A member of the hepadnavirus group. Circular partially double-stranded DNA viruses, the + strand not complete. Replication involves a reverse transcriptase. endemic in the human population and hyperendemic in many parts of the world. Complete Dane particle 42 nm, 28 nm electron dense core, containing HBcAg and HBeAg. The coat and the 22 nm free particles contain HBsAg At least 4 phenotypes of HBsAg are recognized; adw, adr, ayw and ayr. The HBcAg is of a single serotype Endemic in the human population and hyperendemic in many parts of the world. Hepatitis B virus (HBV) has been classified into 10 genotypes (A-J). Genotypes A and C predominate in the US. However, genotypes B and D are also present in the US. Genotype F predominates in South America and in Alaska, while A, D and E predominate in Africa. Genotype D predominates in Russia and in all its prior dominions, while in Asia, genotypes B and C predominate. It has not yet been possible to propagate the virus in cell culture.

Hepatitis B Virus Antigens DNA to RNA intermediate, than replicates genome Use Reverse Transcriptase, Unusual replication Integration into host genome possible HBsAg= virion protein coat HBcAg= virion core antigen HBeAg= minor component

HBV : Structure

HBV Structure & Antigens Dane particle HBsAg = surface (coat) protein ( 4 phenotypes : adw, adr, ayw and ayr) HBcAg = inner core protein (a single serotype) HBeAg = secreted protein; function unknown

Open Reading Frames Genome of HBV There are 4 open reading frames derived from the same strand (the incomplete + strand) S - the 3 polypeptides of the surface antigen (preS1, preS2 and S - produced from alternative translation start sites. C - the core protein P - the polymerase X - a transactivator of viral transcription (and cellular genes?). HBx is conserved in all mammalian (but not avian) hepadnaviruses. Though not essential in transfected cells, it is required for infection in vivo. Genome of HBV

HBV Replication Reverse transcription: one of the mRNAs is replicated with a reverse transcriptase making the DNA that will eventually be the core of the progeny virion RNA intermediate: HBV replicates through an RNA intermediate and produces and release antigenic decoy particles. Integration: Some DNA integrates into host genome causing carrier state

HBV replicative cycle

Hepatitis B Virus Characterisics HBsAg is related into bloodstream as independent particle (not always associated with DNA in virions); aka Dane particle Bloodstream HBsAg & HBeAg are best indicators of active infection Ab can block binding of virions to hepatocytes, but large amount of antigen in bloodstream inactiveate it

Hepatitis C Virus

HCV Structure RNA virus: Single-stranded Positive-sense 9400 nucleotide Virion: Enveloped Icosahedral 40-60 nm Pathogenicity: Cirrhosis possible Hepatocellular carcinoma No proviral integration

In hepacivirus genera: Part of Flaviviridae family of viruses, Enveloped, icosahedral, Single stranded RNA virus Associated with both human and animal disease 3 genera: pestiviruses (cattle, pigs), flaviviruses (Dengue, Yellow fever, Zika), hepaciviruses (HCV) In hepacivirus genera: Classified into six major types and multiple subtypes

HCV Genome HCV is RNA virus: mutates quickly 9400 nucleotide, single ORF Codes for a viral polyprotein about 3000 aa in length E1, E2 in hypervariable region – changes often Allows for evasion of host immunologic response E2 binds to CD81 on liver NS5A inhibits PKR PKR is effector of host antiviral defense pathway eIF2=translation initiation factor

HCV Transmission Shared injection (IVDUs) Blood transfer Sex Mother to child

HCV is a factor for progressive liver diseases such as chronic hepatitis, cirrhosis and hepatocellular carcinoma WHO estimation of HCV prevalence, suggests that there are 170 million HCV-infected patients worldwide (up to 3% of the worlds population) and about 3 to 4 million people are newly infected each year The seroprevalence of HCV in general population of Iran was reported as 0.5 to1 %, but increase to 20% and even 60% in multiple transfused patients with thalassmia

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