15 - hepatitis B, D - notes.docx

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Molecular Genetics and Microbiology
Alan Cochrane

Hepatitis D – parasite on hepatitis B Outside of virus identical to hepatitis B virus – envelope and inserted into env are surface antigesn of hepB - hepB have predominance of large antigens - hepD predominantly has small antigen on its surface - difference from the interior - virion capsid structure – partially dsDNA - hepD – viral RNA that is single stranded that is circular and negative sense - two antigens in surrounding genome, called delta antigen large and delta antigen small D piggybacks on B - virus consists of lipid bilayer - 70% base paired – self-complementary to a lot of itself – have end loops - Viroid element o Commonly found in plants o Infectious nucleic acids o Does not need hepB to replicate itself – just need hepB to allow assembly of virion particle to allow transmission from one cell to next, from one host to the next - Transmission by the same route – sex, exposure to infected blood, perhaps within families with high incidence of hepB and D Geographic distribution – similar to hepB - Impact of infection depends on when you acquire the virus - Left – both simultaneously – majority fully recover and have immunity to both agents - Right – if HBV carrier (chronic) – can be superinfected with HDV – can lead to chronic HBV and HDV infection – leads rapidly to cirrhosis Outer coat similar to hepB – enter same way as hepB – use S protein to dock receptor on hepatoctye to drive fusion of two membranes - Releases viral core that contains delta antigen large and small – released into cytoplasm, where it goes into nucleus and where it replicates – expresses Make mRNA to reduce delta antigens – replicate its circular genome – unclear how - Virus does not coe in with its own polymerase, does not use hepB polymerase - It’s an RNA virurs, but uses host RNA Polymerases ****** o 1, 2, and 3 – normally recognize dsDNA to initiate transcription but somehow virus recognized now by RNA polymerase 2 and 1 – partically doublestranded genome binding RNA polymerase of host – host transcribes RNA to make single stranded RNA that produce mRNA – polyadenylated, exported into cytoplasm to generate delta antigens o Some debate about how genome gets replicated – current acdcepted model is – genome gets transcribed in two places – in nucleoplasm – o If enter nucleolous, transcribed by rNA polymerase I o Rolling circle method of generation – generates anti-genome, shunted back into nucleoplasm – transcribed by RNA polymerase two – that’s how it gets amplified - Genome read by RNA polymerase II – transcribed, hits polyadenylation signal – RNA polyadenylated – RNA polymerase two – recruits factors required for polyadenylation at the same time – Othe rproblem - Making long liniear RNAs by RNA Polymerase two – not capped, not polyadenylated – susceptible to degradation by host machinery – avoid this how? - Genome coming in is circular – transcribe by RNA polymerase I, to make long strands – red ball is ribozyme, which is a confroamtion of RNA able to cleave and ligate in cis or trans - RNA gets transcribed into this sequence – folds into secondary structure, or tertiary structure that cleaves at this point to form precise ends – take ends and because cleavage is ame reaction as ligation and ligate them – form covalently closed circular antigenome - Transcribe, make structure, cleaves itself, repositions it, so basically ligate, have covalently closed template for transcription – make RNA after 6 – two copies of ribozyme – g
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