L6 Hepatitis C Virus Flashcards
(52 cards)
What does immune-screening involve?
Using the human antibodies to find the viral proteins
How can Hepatitis C virus (HCV) be transferred?
By transfusion of blood or blood products, as well as non-sterile medical measures
HCV infection can cause…
chronic liver inflammation, leading to cirrhosis and liver cancer
What percentage of infected people can develop a chronic life-long infection?
70-80%
What cancer is commonly associated with HCV infection?
Hepatocellular carcinoma (HCC)
Features of HCC
- highly malignant tumour with poor prognosis
- high levels of anti-HCV present
- 97% have cirrhosis
Which genotype is associated with higher rates of HCV-associated HCC?
Genotype 1b
Briefly explain how erythrocyte destruction can occur when a Rh- woman has given birth to a Rh+ baby
- Erythrocytes from a Rh+ foetus leak into the maternal circulation, usually during birth
- This stimulates the production of anti-Rh antibody of the IgG class postpartum
- During subsequent pregnancies, IgG antibodies are transferred across the placenta into the foetal circulation
- If the foetus is again compatible, the antibodies cause erythrocyte destruction
What can be used to treat Rhesus negative mothers who have had a Rhesus positive baby?
Anti-D immunoglobulin (available since 1970)
It eliminates the Rh+ erythrocytes and prevents sensitisation
Which genotype is the most resistant to therapy?
Genotype 1a
Around how long does an acute HCV infection last?
from 0-24 weeks, often remains undetected
What are the most important causes of mortality in end-stage chronic Hepatitis C (CHC)?
cirrhosis and hepatocellular carcinoma (HCC)
HCV structure
- enveloped virus
- positive-sense ssRNA genome
- capsid
- virus-encoded proteins present in lipid bilayer
HCV is part of which family?
HCV is a Hepacivirus (Flaviviridae family)
What is the IRES in HCV?
IRES = internal ribosomal entry site
Contains regions of dsRNA - used by virus to bind ribosomes and start translation
How does HCV enter the cell?
HCV binds to hepatocyte cell surface protein receptors and enters the cell by receptor-mediated endocytosis
Examples of hepatocyte cell surface receptors to which HCV bind
- LDLRs on the basolateral hepatocyte surface
- CD81
- tight-junction proteins claudins (CLDN-1 and OCLN)
Innate immunity receptors involved in HCV detection
- TLR7: detects ssRNA (endosome)
- TLR3: detects dsRNA in replicating ssRNA viruses
- (RLR) RIG-1 (retinoic acid-inducible gene 1) detects ssRNA (cytoplasm)
- PKR (RLR) detects dsRNA (in HCV genome, it detects dsRNA in IRES at 5’ end)
Detection of HCV RNA leads to?
activation of transcription factors (NF-κβ, IRF3, IRF7), which leads to the production and secretion of cytokines and Interferons (anti-virals)
What is the HCV protease that inhibits the immune system in a number of different ways?
NS3-NS4A
How does NS3-NS4A inhibit the immune system?
- cleaves HCV polyprotein several times to liberate NS proteins
- blocks RIG-1 signalling by cleaving MAVS from intracellular membranes to prevent signals (results in lower IFNs)
- blocks TLR3 signalling by cleavage of TRIF
- NS3-NS4A and E2 protein blocks PKR activity
HCV genotypes
(i) Genotypes 2 and 3: highest IFNα treatment response rates, 70-80%
(ii) Genotypes 1 and 4: only curative in 40-50% of cases
IFN induces the expression of 100s of…
IFN stimulated genes (ISGs), that have anti-viral and immuno-modulatory activities
Genotypes 1 and 4 induce high levels of __ in infected patient’s liver before therapy, resulting in a less effective IFN response.
hepatic ISGs
