L13/14 - HepC (1) Flashcards
What Hep viruses are non-envelped?
HepA
HepE
What Hep viruses are enveloped?
HepB
HepC
HepD
How are non-enveloped Hep viruses transmitted?
Enteric
How are enveloped Hep viruses transmitted?
parenteral
Function of hepatocytes?
Metabolise carbs, fats, proteins
produce serum components
Detoxify
Produce Bile
Which Hep viruses are released into the blood?
Hep B/C/D
envelopes cannot handle acidic environment of bile
Which Hep viruses are released into the bile?
Hep A/E
stable within acidic/detergent environment
How does blood enter the liver?
Sinusoids
How many genotypes of HCV?
7
What genotypes of HCV are most common in W. Europe?
Type 1-3
Why is there a high incidence of HCV in Egypt?
Treatment campaign Schistosomiasis in 1960s
re-used glass syringe, emetic tartar
Original name fo HCV?
NANBH
How was HCV cloned?
serum centrifuged RNA extracted Reverse transcribed clone into lambda bacteriophage Infect E.coli with bacteriophage library
imprint plate using nitrocellulose membrane
probe membrane with antiserum from infected patients
What family is HCV a member of?
Flaviviridae
Structural proteins of HCV?
Core
E1
E2
(p7)
Non-structural proteins of HCV?
(p7) NS2 NS3 NS4A NS4B NS5A NS5B
What is the p7 protein of HCV?
ion channel
What % of acute hepatitis cases lead to chronic liver disease?
<85%
What are ALT?
Allanine amino transferase - usually present in hepatocyte
What does elevated levels of ALT cause?
Cirrhosis and potentially Hepatocellular carcinoma
Are levels of ALT always the same?
titres can fluctuate over years - virus not cleared
What is liver fibrosis?
scar tissue in liver underneath hepatocyte
restricted blood supply
Link between HCV and insulin resistance?
HCV disrupts pathway and increases cytokine production of IL18 and TNF-a
What other effects does insulin resistance have on the body?
Type II diabetes
Reduced antiviral response
Increased incidence of HCC
Accelerated fibrogenesis
Link between HCV and lipid metabolism?
Core associates with lipid droplets
lipid accumulation
NS5A - dramatic increase in amount of lipid droplet
Hepatocytes are lipid producers - transported ELSEWHERE
What processes are increased in lipid metabolism during HCV infection?
Lipogenesis
What processes are decreased in lipid metabolism during HCV infection?
Lipoprotein secretion
Fatty acid oxidation
What fatty liver condition does HCV lead to?
Steatosis
What is Steatosis?
effects of core and NS5A proteins
enhanced by lifestyle
Genotype-specific
Which genotype does Steatosis have a higher incidence in?
Genotype 3
What is HCC?
Hepatocellular carcinoma
How does HCC develop?
Chronic liver injury
Inflammation
Increased cell turnover
Oxidative DNA damage
How is the liver repaired?
Move out fo G0 into cell cycle
divide to repair liver
What does Wnt/B-cantenin control?
gene expression
What molecular requirements INCREASE for development of HCC?
Cell cycle
Vascularisation
Gene expression
What molecular requirements DECREASE for development of HCC?
apoptosis
What does p53 control?
apoptosis
What does TGFb (retinoblastoma oncogene) control?
apoptosis and Cell cycle
What HCV proteins are involved with p53?
NS5A
Core
NS3
What HCV protein are involved with TGFb?
NS5A
Core
What HCV proteins are involved with Rb?
NS5B
What HCV proteins are involved with Growth factors and Wnt/B-cantenin?
NS5A
