Week 2: Hepatitis viruses Flashcards
1
Q
Hepatitis
A
- An inflammatory process involving the liver
- In its early stages, hepatitis may cause flu-like symptoms including malaise, fever, muscle aches, loss of appetite, nausea, voming, diarrhoea + jaundice
- Up to 7 viruses cause hepatitis through damage of hepatocytes
2
Q
Hepatitis A Virus (HAV)
A
- Also known as infectious hepatitis
- Largely preventable
- Can become fulminant, but rarely, with healthy individuals completely recoviering within weeks/months without long term complications
- Non-enveloped spherical positive stranded RNA virus (Class 4)
- Encodes polycistronic mRNA + infectious genome RNA, translation of genome RNA into mRNA forms polyprotein product that is cleaved to form mature proteins
- Transmitted rapidly in overcrowded + unclean living conditions
3
Q
HAV genome structure
A
- Consists of 3 loci and genome ends with regions that aid in the translation and synthesis process
- The 3 loci:
+ P1-2A
+ 2BC
+ P3 - NTRs:
+ 5’NTR
+ 3’NTR + polyA - 2BC + P3 encodes for products involved in the replication complex
- Remaining genome encodes a single polyprotein of between 2100-2400 amino acids
4
Q
P1-2A (HAV)
A
- VP4, -3 and -1 which encode for the procapsid
- 2A encodes for the receptors
5
Q
2BC (HAV)
A
- 2B = Encodes for vesicle formation
- 2C = Encodes for helicase that is then contributed into vesicle formation
6
Q
P3 (HAV)
A
- 3A encodes for membrane anchor
- 3B encodes for primers
- 3C encodes for protease
- 3D encodes for polymerase
7
Q
5’ + 3’ NTR
A
- 5’ UTR
+ 600-1200 bases
+ Key in translation, virulence + possibly encapsidation
+ Contains a clover-leaf secondary structure known as the Internal Ribosome Entry Site (IRES)
+ Has a covalently attached small basic protein (VPg ~23aa) - 3’ UTR
+ 50-100 bases
+ Important in negative strand synthesis
+ Capped by PolyA tail
8
Q
Long/Short forms of TIM1 gene in humans
A
- May have been driven by viral infection
- The long form is more likely to be infected by HAV severely, but can have an excellent immune response
- Short from is less likely to be infected by HAV severely, but predisposes to allergy + asthma
- TIM1 gene is found in ch5q23q35
- Long form is caused by a 6aa insertion in Tim1/HAVCR1
9
Q
Prevention of HAV
A
- Largely preventable by following rules of good hygiene + avoiding crowded, unhealthy living condition
- HAV vaccine is recommended to travellers, sexually active individuals + people in high risk occupations
10
Q
Hepatitis B Virus (HBV)
A
- Also known as serum hepatitis
- Spreads via infected body fluids + immune response is triggered by the Au antigen
- 90-95% of patients recover completely within 6 months, but patients can develop chronic hepatitis + liver cirrhosis + become life-long carriers
- All blood, organ + tissue donations are screened in developed countries
- Doesn’t grow well in tissue culture
11
Q
Unstable genome in HBV
A
- Due to its small size, HBV is prone to making mistakes, having an inefficient structure production, so to compensate, the virus particle is replicated in large numbers
- Contains partial dsDNA + RNA-dependent DNA polymerase
- Known as a para-retrovirus due to reverse transcriptase (RT)
- As a result, can be treated with RT inhibitors
12
Q
Gapped dsDNA in HBV
A
- Made up of 3 major transcripts of 3.5kb, 2.4kb + 2.1kb, each with different 5’ ends + same 3’ ends
- 4 known genes:
+ COre protein
+ Polymerase
+ Surface antigen
+ Transactivator of viral transcription - Pre-S1 + Pre-S2 make up the Pre-S entitiy in the viral envelope
13
Q
HBV classification
A
- Class 7 - dsDNA with RNA intermediate
- Part of hepadnaviridae
- Have some of the smallest genomes of all known viruses, consisting of 2 uneven strands of DNA - A negative and positive sense strand
14
Q
HBV protein designation
A
Protein-Size in genome-Function
- Core: p21, Core particle structure + kinase activity
- Pre-core (HBsAg): p25-16, Pre-core/core protein that is cleaved into HBsAg
- Surface: p24/gp27, envelope protein (The main vaccine target)
- Pre-S2: HBsAg + 55aa, HBV binding + entry
- Pre-S1: Pre-s2 + 119aa, HBV binding + entry
- Polymerase: p70, Viral replication/reverse transcription
- X-protein: 154aa, Trans-activation
15
Q
Prevention/therapy of HBV
A
- We now use recombinant HbsAg vaccine produced in yeast
- Effective vaccination campaigns can save ~ 1 million lives per annum + eradicate the virus, since there is no animal reservoir
- Alpha interferon is used for chemotherapy of chronic HBV infection, but it is expensive and only 30-40% of chronic carriers respond to this treatment
- Lamivudine + others are RT inhibitors used for therapy of chronic HBV infection
16
Q
Hepatitis C Virus
A
- Currently rising in cases, has no vaccine and difficult to treat
- Shares charactersistics of HAV + HBV
- Transmitted bia IV drug use + shared needles, maternal transmission + blood trasnfusion + some sexual contact
- Low fatality rate, but high chronic infection likelihood
- High mutation rate
17
Q
Features of HCV infection
A
- Incubation period ~ 6-7weeks
- Acute illness (jaundice) - Mild
- Low fatality rate
- Chronic infection: 75%-85%
- Chronic hepatitis: 70%
- Cirrhosis: 10%-20%
- Mortality from CLD: 1%-5%
18
Q
HCV genome for structural products
A
- Core: Functions for ER localisation/Nucleocapside formation
- E1: ENvelope/Fusion domain
- E2: Envelope/Binding to celling receptor/Fusion domain
- P7: Ion channel
19
Q
HCV genome for non-structural products
A
- NS2: Autoprotease NS2/NS3
- NS3: NTPase/helicase/NS2-NS3 autoprotease
- NS4A: Cofactor of NS3/NS4A protease
- NS4B: Membranouse web formation
- NS5A: Replication complex formation
- NS5B: RNA-dependent RNA polymerase
20
Q
Classification of HCV
A
- Flavivirus group
- Linear ss RNA, positive sense (Class IV), 10000-11000 nucelotides long
- Uniform virion shape, spheroidal + enveloped, 40-60nm in diameter
