33. Hepatitis B Virus Flashcards
3 main proteins in HBV
- HBsAg
- HBeAg
- HBcAg
2 forms of DNA in HBV
- cccDNA
- RC DNA
What does cccDNA stand for?
covalently closed circular DNA
what does RC DNA stand for?
relaxed circular DNA
how is HBV transmitted? (2)
- blood
- sexual
what type of virus is HBV?
orthohepadnavirus
genome of HBV
dsDNA with gaps
does HBV cause chronic infection?
yes
common incidence of transmission for HBV
vertical –> mother to child
baltimore classification
7
How many people are chronic HBV carriers? how many die of HBV per year?
248 million chronic HBV carriers
750,000 die of HBV per year
2 diseases that chronic HBV cause?
- liver cirrhosis
- hepatocellular carcinoma
4 stages in the course of chronic HBV infection
- immune tolerant
- immune clearance HBeAg-POSITIVE chronic hepatitis
- inactive carrier case
- reactivation HBeAg-NEGATIVE chronic hepatitis
what happens in stage 1: IMMUNOTOLERANT
- high levels of eAg, sAg, DNA
- low levels of liver enzymes
NO aggressive immune response/inflammation in liver
what happens in stage 2: immune clearance HBeAg-POSITIVE chronic hepatitis
eventually, immune system will take over
- high levels of eAg, liver enzymes
- fluctuations in HBV, sAg
what happens in stage 3: inactive carrier state
some ppl will lose eAg expression and develop anti-eAg antibodies
- due to mutation in core promoter during chronic replication in liver to prevent eAg expression
- but sAg and DNA are still produced
aka QUIESCENT
what happens in stage 4: reactivation eAg-NEGATIVE chronic hepatitis?
virus reactivated and enhanced
- DNA and sAg increase
which viral antigen is always present?
sAg
4 viral factors associated with HBV disease progression
- persistence of eAg
- persistenc of HBV DNA
- HBV genotype C, rather than genotype B
- core promoter mutation (loss of eAg)
4 environmental factors associated with HBC disease progression
- alcohol
- smoking
- aflatoxin
- HCV, HDV, HIV co-infection
5 host factors associated with HBV disease progression
- male
- old
- recurrent alanine aminotransferase
- cirrhosis
- diabetes
3 diff HBV particles? which is infectious?
- Dane particles –> infectious
- Filaments
- Spheres
why does HBV express large amounts of S antigen?
to exhaust the immune system and make it defective
why are there non-infectious HBV particles?
act as decoy to exhaust the immune system and make it defective
2 roles of cccDNA
- template for RNA pol II to make viral mRNA for viral proteins
- transcribed by RT to make RC DNA copies for packaging
2 receptors that HBV binds for entry
- NTCP
- EGFR
What does NTCP bind on the virus?
binds pre-S1 region on LARGE envelope proteins
what are the 3 envelope proteins? which type of particle has all 3?
large, middle, small
dane particles have all 3
why is there tropism for the liver?
NTCP is present only on hepatocytes for bilirubin export
what happens once infectious particles bind NTCP and EGFR? 5 steps
- capsid with RC DNA enters
- RC DNA transported to nucleus
- polymerases and ligases fill in the gaps to make cccDNA
- cccDNA makes subgenomic RNA and pregenomic RNA
- pregenomic RNA is recognized by RT to make RC DNA for packaging
what type of polymerase is RT?
DNA pol
describe the virion DNA
+ strand is incomplete, - strand is full
how many promoters?
4
how many terminators?
1