CSB351Y1 Lecture Notes - Lecture 40: Hdv, Hbsag, Circular Rna
26 May 2018
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Lecture 40
• Hepadnavirus (hepatitis) – 3.2kb ds/ss DNA, enveloped, more empty viruses than those with DNA in them
• Dane particles are 42-47nm spherical (T=3), enclosed by host-derived lipid-containing envelop and contains DNA
- Viral envelop has three surface proteins/antigen HBsAg (L, M and S), surrounds nucleocapsid core (22-25nm)
- Core particle associated with viral DNA polymerase to repair partially single-stranded region of viral genome
- Decoys (20nm) that do not contain viral DNA – avoids detection
Genomic organization
• S (surface protein), P (polymerase), C (core), X (unknown) – -strand complete of DNA overlaps but +strand not
• ’ egatie stad has ius-encoded covalently attached protein
• ’ positie stad liked to RNA oligoucleotide sees as teplate for synthesis of viral mRNA transcripts
Life cycle
• Releases core into host, core goes into nucleus and DNA is circularized into cccDNA (covalently closed)
• Use host machinery to repair the missing space on positive strand → cccDNA
• Transcription → RNAs produced , exit into cytoplasm → translation → replication/re-enter into nucleus to form
cores around new replicating genomes → leave nucleus, Sproteins produced from ER and buds out of host cell
HBV replication
• pgRNA ’ epsilo ste-loop attract polymerase/rtranscriptase of virus → synthesizes –strand from +strand
• From DR1 to DR1 on the other end, transcribes but polymerase has RNaseH activity (degrades RNA behind it)
• ’ esistat to RNaseH actiity ad RNA oligoe taslocated to DR ad used fo pie for +strand synthesis
Distribution and epidemiology
• 2 billion people infected (1/3 of human race) with HBV but geographic distribution is uneven (sub Saharan
Africa, Amazon, south east Asia) and 600 000 die each year
- Western countries – mostly in adults (sexual contact or through skin), worldwide, HBV most common cause
of chronic liver disease in humans. Latent for 6-24 weeks
Transmission and tropism
• Persists in blood, sexual contact, skin punctures, IV drug abuse, inoculation with contaminated blood, saliva, in
uteo o othe’s ilk
• Symptoms – half of all hae o syptos o do’t ealize adults hae oe syptos tha childe
- Similar to flu, jaundice, appetite loss, nausea, fatigue, itching, pain over liver
Pathogenicity
• HCC may develop after many years of HBV infection and can have cirrhosis
- 25% adults who become chronically infected at childhood, later die from liver cancer/cirrhosis (scarring)
- Leading to cirrhosis, there may be carcinogenic without oncogenic action of virus
• One mode of HBV pathogenesis – initiate immune complex disease, related to HBsAg-anti HBs complex
Prevention - avoid contact with infected individual, screen blood to avoid spread via medical transfusion and vaccination
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Document Summary
Lecture 40: hepadnavirus (hepatitis) 3. 2kb ds/ss dna, enveloped, more empty viruses than those with dna in them, dane particles are 42-47nm spherical (t=3), enclosed by host-derived lipid-containing envelop and contains dna. Viral envelop has three surface proteins/antigen hbsag (l, m and s), surrounds nucleocapsid core (22-25nm) Core particle associated with viral dna polymerase to repair partially single-stranded region of viral genome. Decoys (20nm) that do not contain viral dna avoids detection. Distribution and epidemiology: 2 billion people infected (1/3 of human race) with hbv but geographic distribution is uneven (sub saharan. Africa, amazon, south east asia) and 600 000 die each year. Western countries mostly in adults (sexual contact or through skin), worldwide, hbv most common cause of chronic liver disease in humans. Similar to flu, jaundice, appetite loss, nausea, fatigue, itching, pain over liver. Pathogenicity: hcc may develop after many years of hbv infection and can have cirrhosis.
