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24 Cards in this Set
- Front
- Back
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What kind of a virus is Hep B?
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-partially ds DNA
-circular -3.2 kb (small) -requires a RT step of pregenomic RNA -member of hepadnea family -specific for humans, ducks, snow goose, woodchucks, chimps |
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How is Hep B transmitted?
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-Blood
-Sexually |
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What are the diseases ass't with this virus?
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Liver cancer
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What treatment is available for Hep B?
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-Vaccine available for Hep A and Hep B
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What's special about transcriptonal processing of Hep B?
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-No splicng
--> More clever use of ORFs |
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What genomic stages does Hep B go through?
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DNA--> RNA--> DNA
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What is the structure of the virus?
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large surface proteins, middle surface protein, small surface protein, core protein, polymerase, HBV DNA.
-The large, middle and small surface ptns are env ptns -Pol is covalently attached to the DNA |
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How can Hep B infection be prevented?
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-Develop antibodies agains surface antigens of Hep B env after natural infection
-Get vaccine before infection -Injection of anti-HBV immunoglobulins after post-exposure (mother-child transmission) |
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What are treatments available vs HBV?
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-IFN: targets viral ptn
-3TC: used for HBV and HIV, but virus quickly selects against this, but good because it can be used if someone infected with both viruses -Tenofavir: works well vs HBV, might also work vs herpes and CMV Nucleoside inhibitors are very specific (3TC is an exception) |
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What is the life cycle of HBV?
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Attachment
Entry Nuclear Transport -DNA virus goes into the nucleus but is not integrated into the genome, .: can't target this step -Virus recruits cell enz to transcribe RNA and cell enz to transport the RNA to the cytoplasm (NO evidence of splicing) -Viral hairpin structure important for attachment of the core structure -After transported to the cytoplasm, can do translation -Reverse Transcription then takes place (quite late compared with HIV) -Assembly of virions, budding and maturation (last mechanisms not well understood) |
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Where does HBV replicate the best?
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In the liver
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How is DNA synthesis completed?
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When uncoated, the nucleocapsid is transported to the nuclear mb and genome is brought into the nucleus
To make closed, circular DNA: (-) strand first synthesized, (+) strand is linearized 1) extension of the plus-strand DNA 2) removal of the P protein and the RNA primer (P protein is attached the 5’ end) Protein primed reaction (RT) 3) ligation of the resulting 3’ OH and 5’PO4- ends. -1st step done by virus, while rest of steps done by cell enz -5' cap is cleaved by nuclease -DR1 and 2 (direct repeats) within the circular dsDNA are imp for RT (has an unknown ptn linked to RT/oncogene) |
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How is HBV transcribed?
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-HBV genome directs the synthesis pregenoic RNA and mRNAs
-Cell Pol II recognizes 4 promoters: PreS1, PreS2, C and X -Transcription enhanced by 2 enhancer seq (EnhI and II) which provide binding sites for cell TF (including TFs specific to the liver) .: enhancers regulate transcriptional levels |
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What are pre-S1/S2 and S?
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3 dif mRNAs generated from the same ORF
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What is the epsilon stem loop important for?
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Required for RT and genome entry into the virion
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What are the 4 ORFS?
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1)Surface proteins (3mRNA, PreS1, PreS2 and S)
2)Core proteins (2 mRNA, PreC and C) 3)Polymerase (P protein, RT (RNA- and DNA-dep-DNA-Pol) pgRNA 4)Regulatory protein (X protein) (1 mRNA) |
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What's the role of the X ptn?
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-Implicated in liver cancer
-Stimulates viral transcription so probably a TF |
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What is the core ptn for?
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Packaging of the HBV genome into the virion
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What are the surface ptns for?
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3 Surface ptns
-involved in HBV envelope formation |
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What is the P ptn (polymerase) for?
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Required for replication
-Has RNA- and DNA-dep-DNA-pol -Has RNAse H activity to degrade RNA intermediate |
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Are there conserved regions between HIV and duck-HBV?
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Yes, but ptns are dif
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What primes DNA synthesis? What happens during DNA replication?
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Tyrosine on N-terminus
-P ptn binds to Tyrosine on the epsilon sequence and 4 nucleotides are synthesized -When 5' end of epsilo seq is primed, it can induce strand transfer -Newly synthesized DNA has homology to DR1 -RNAse H activity starts after th strand transfer to the primed strand (it stops degrading when 18 nt left, cuz those nt will act as a primer) -2nd strand transfer (requires cellular factors) |
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Why is HBV partially ds?
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DNA synthesis stops 50-80% of the time (might be so that it fits better in the virion)
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What are the mechanistic dif btw HIV and HBV?
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HIV
-has 2 RNAs in it, which confers genetic variability. -Integrated into the genome -50-100 molec/core -host tRNA primes (-) strand HBV -Partially dsDNA -RT confers genetic variability -Not integrated into the genome -Polymerase covalently attached to genome so only 1 molec/core -P ptn primes (-) strand |
