Hepatitis B+D Flashcards
Is the scale of difference for HepB, bigger or smaller than for HepC?
Much smaller
What type of genome does HepB have?
DNA, enveloped virus
What are the sub virus particles of HepB used as?
As a decoy system, they dont have a capsid etc., like the actual virus
How many open reading frames are there?
4
What length is pre-genomic RNA vs the genome length?
Pre genomic RNA is 3.5kb long
Genome is only 3.2kb long
Where does pregenomic RNA start transcription?
DR1 region
Surface antigen mRNA start transcription?
PreS1 region
What does HBV bind to for entry?
Two receptors (NCTP - bile acid transporter, EGFR)
What is the translocation process of HBV replication?
Internalises through an endosome, internalises into a vesicle, fuses when pH changes
What is the conversion of rcDNA to cccDNA process with HBV?
Releases capsid protein containing partially dsDNA genome
Goes to nuclear membrnae, through pore, degrades capsid
Releases DNA into nucleus, gets converted into ccc DNA (covalently closed circular DNA)
What happens to HepB following CCC DNA conversion?
MRNAs encoding different genes are made and they go to cytoplasm and interact with ribosomes to produce viral proteins
Why is the surface antigen different to most other viral proteins in the processing?
Surface antigen is processed separately
What are the two consequences following viral prtoein production?
Firstly sub virus particles are made using different secretion pathway to assembly of a virus particle
Independent expression system means that the virus can evolve to regualte to increase expression of those SVPs to control expression through multi vesicular body
What is the final part of the HepB life cycle converting back to DNA +?
RNAse, pre-genomic RNA expressed from nucleus into cytoplasm
This gets reverse transcribed inside the capsid back into a copy of DNa which is identical to the one which has come in
What does HBeAg do?
Expressed with active, high levels of replication, suppresses JAK/STAT signalling to reduce effectiveness of interferon signalling
How many forms does core antigen have?
Two - one is called core antigen , one is E antigen
How does open reading frame lead to core protein?
Open reading frame, has core protein and start codon. Encodes piece of mRNA to make E antigen, whole mRNA is E antigen that makes the protein. Then it is cleaved to make core, so get initiation and some E antigens get cleaved into core protein. It dimerises and changes conformation and allows it to be packaged into new particle
How do pre-core mutations occur?
E antigen is highly immunogenic, applies large selection pressure for mutations. Mutated mRNA that is produced has a mutation, this stops E antigen being expressed. These are pre core mutants
What is acute hepatitis?
Three phases of illness:
- prodrome malaise: fatigue, fever, vomiting etc.
- icteric phase: dark urine, yellow eyes, light coloured stools
Convalescence gradual recovery is normal
Why are anti-HBs seen so much later after clearing the virus?
When you remove SPVs, they are soaking up antibodies, so now they dont mop up anymore antibodies now they have gone so only see surface antigen antibodies once the virus is gonna
What happens in acute liver failure?
Symptoms similar to those of acute hepatitis to begin with
But more severe liver damage, bleeding tendency, small liver, brain oedema, altered behaviour and consciousness
What are markers of liver damage?
AST and ALT
What percent of people that have chronic HepB result in hepatocellular carcinoma?
1-5%
What phases of chronic hepatitis B need antiviral drug treatment?
Immune active phase, cirrhosis in any phase, reactivation phase
When do you have lifelong treatment for HepB?
Cirrhosis or APRI >2.0
What is current treatment for HDV?
Is interferon alpha and bulevirtide
