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

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

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

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

6. 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.

8. 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

9. 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.

10. 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

11. HBV : Structure

12. 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

14. 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

15. 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

16. HBV replicative cycle

17. 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

18. Hepatitis C
Virus

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

21. 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

22. 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

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

26. 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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