Hepatitis C Flashcards
What genome does HepC have?
Positive sense, single strand RNA virus
What is transmission of HepC solely through?
Contamination with infected blood
What percent of HCV infections roughly are acute?
25% of infections
What are 3 markers of acute infection?
- Serum alanine aminotransferase (ALT)
- HCV RNA
- Anti-HCV (ELISA)
What does ALT indicate?
Liver damage, indicates hepatocyte necrosis
What is compensated cirrhosis?
Build up of scar tissue but doesn’t affect function of liver, so may be asymptomatic
What is required for patients with severely decompensated cirrhosis and/or hepatocellular carcinoma?
Liver transplantation
Why if you treat someone of HCV do they still have a high risk of developing liver cancer?
Gene expression patterns have changed
What co-infections with HCV can you have?
HIV, HBV
What does RIGI sense for HCV?
SsRNA, triggers anti viral state
What does MDA5 sense?
Replicate intermediates
How does HepC evade immune system?
Virion incorporates host proteins CD59 and CD55
Virion associates with lipoproteins
What happens in chronic HCV infection to T cells?
Are functionally impaired, decreasing proliferation, cytokine production and cytolytic activity
What does ribavirin as a treatment do?
Affects the synthesis of guanine, makes it less abundant in cells so that when you get genome replication, you are missing a lot of one of your bases to try generate more RNA
What was the issue with using interferon and ribavirin together?
Got a lot of side effects, lots of people on this therapy couldn’t tolerate it
What are the replication inhibitors?
DAA
Epclusa
Zepatier
Mavyret
What are the 3 classes of DAAs (directly-acting antivirals)
NS3 inhibitors - NS3 forms protease, cleaves up polyprotein
NS5B inhibitors - RNA polymerase, interfere with production of proteins
NS5A inhibitors - NS5A is key player in assembly of viruses, so inhibiting this is a clever part of virus lifecycle being affected
What should a HepC vaccine target?
Envelope proteins - elicits a neutralising Ab response
Non structural proteins - T cell response
What are the HCV vaccine challenges?
Large genetic diversity of HCV species
Lack of robust in vivo models
