Hepatitis C Virus Flashcards
What type of virus is Hep C
A flavivirus
How long does seroconversion take
3-6 months
How long is the latency of Hep C
2-9 weeks
How many people are affected by Hep C
71 million
0.1% UK
1.4% US
14% Egypt
What % of acute and chorinic hepatitis is caused by Hep C
20% Acute
70% Chronic
What are the outcomes of Hep C Infection
10-30% Clear
70-90% get chronicn infection
What are the soruces of Hep C Infection
60% IVDU 15% Sexual Contact 10% Unkown 10% Transfusion 4% Occupational 1% Household transmission
How many genotypes of HCV are there
7
What genotypes of HCV Are prevlanet where
1 - mainly Americas, Japan, Northern europe
3+6 = South and SW Asia
4+5 = Predominant in Africa
7 = rarely seeen in Africa byt not of clinical importance
What % of hepatocytes are infected by HCV
5-19%
What is teh half life of HCV
2-3 hours
What is the structure of HCV
50nm diameter
9.6kb +ve sense RNA genome
What does the polyprotein encode
Structure (Core , E1 and E2) Non Structural (p7, NS2, NS3, NS4A, NS4B, NS5A, NS5B)
Where does HCV Replicate t
The cytoplasm
What are the receptors for HCV
E1/E2 bind to SR-B1 and CD81
Also Occludin and Claudin 1 important for binding
Also EGFR and ephrin type 2A receptor
What proteases cleave the HCV polyprotein
Cellular Proteases - signalase
Viral proteases - NS2-NS3, NS3-NS4A
How many proteins are there
10
When does ALT peak
2 months –> coincides with a good T cell response
How do the HCV proteins promote HCC
Core - inhibits apoptosis
NS3 - promotes cellular transformation
NS5A - contains a transactivation domain
How do the HCV proteins perturb the IFN response
Core protein –> inhibits Stat1
NS5a –> generally attenuates IFN production
NS5a and E2 - inhibit PKR –> part of the innate response for binding and responding to dsRNA
Where do ab target
The highly variables E2 region
When are Ab generally detectable by
7-31 weeks –> however they are not maintained for life!
How can persistent HCV infection trigger cell destution
Fas ligand induced apoptosis and TNF alpha and performin based mechanisms for cell destruction
Why does HCV Persist the 3 hypothesis
1) Immune response too weak to clear infection once restablished
2) HCV Proteins suppress the immune response
3) VIral genetic variation
What HCV Proteins supprress the viral imune response
NS3 - blocks IRF3 activation and IFN synthesis
NS5A - blocks PKR
Polymorphisms in what gene promote HCV Clearnce
IL28B –> thsoe iwth C/C have a 2 fold higher chance of clearance than T/T
Name the HCV Protease inhibitors and what they inhibit
Telaprevir and Boseprevir
Inhibit NS3/NS4A proteases –> WORK AGAINST GENOTYPE 1 –> incrases response rates to up to 70%
What is the response to IFN-alpha and ribavarin
50%
Poor response ot type 1
Cost of telprevir and boseprevir
£30,000 per person
What is the NS5B Inhibitor
Sofosbuvir
What is the NS5A inhibitor
Dalactavir
Cost of NS5B inhibitor
£40,000
