Viral hepatitis II

Question 1

Describe the morphology of HCV

Answer 1

• flavivirus
• +ssRNA
• seven genotypes

Question 2

How did screening of HCV-infected donors affect the incidence of acute HCV?

Answer 2

Declines among transfusion recipients and decline among injection drug users

Question 3

What tests are used to test for HCV in blood

Answer 3

2nd gen HCV Ab and RNA tests

Question 4

What are the major targets for antiviral therapy in HCV?

Answer 4

NS3 (protease), NS5A, NS5B (RdRp)

Question 5

Why is HCV challenging to make a vaccine in?

Answer 5

lots of variability between HCV genotypes + quasi species

Question 6

Why is HCV bad? Epidemiology wise

Answer 6

• most acute infections become chronic
• leading indication for liver transplant
• most common blood-borne disease in NA and Western Europe

Question 7

How is HCV transmitted?

Answer 7

• blood (safer now)
• IV drug abuse (most common)
• sexual transmisson
• vertical transmisson

Question 8

How efficient is HCV transmisson?

Answer 8

very - contaminates drug paraphernalia, not just needles

Question 9

Why is HCV bad health wise?

Answer 9

most acute HCV becomes chronic and it is not detected until cirrhosis begins usually

Question 10

What was the therapy for HCV, what is now the therapy for HCV, is it curable?

Answer 10

was = Peg IFN and ribavirin
now = DAA –> cures

Question 11

How was the mouse model of HCV developed?

Answer 11

Crossing Alb/uPA mice onto SCID background –> Alb-uPA/SCID mouse (must be homozygous) –> inject human hepatocytes into mouse spleen –> human hepatocytes migrate to liver –> transgenic mouse thats immunocomprimised and transplanted with human hepatocytes

Question 12

Why did we get rid of IFN treatments for HCV?

Answer 12

IFN causes lots of side effects

Question 13

What an ideal therapy for HCV?

Answer 13

• IFN free
• one-a-day dosing
• few or no side effects
• little or no resistance
• effective for all genotypes

Question 14

Whats a current issue for HCV therapy?

Answer 14

• very costly
• trying to find carriers before it’s too late

Question 15

What are the effects of curing HCV?

Answer 15

• reduces total mortality
• reduces liver-related mortality
• reduces liver cancer from HCV
• renders patients non infectious

Question 16

Is HCV treatment increasing SVR more than new cases are reported? What does this imply?

Answer 16

No - need a vaccine

Question 17

What are HCV vaccine challenges:

Answer 17

1. viral diversity
2. there was a vaccine clinical trial and it failed, so no clinical trails can happen until a vaccine is shown to have efficacy

Question 18

Is there immunity to HCV?

Answer 18

yes - partial: reinfection with a different genotype have lower peak viremina, shorter duration of viremia, and reduced chronicity

Question 19

Why is development of an HCV vaccine important?

Answer 19

cost effective, antivirals are very expensive

Question 20

What is a CHIM study?

Answer 20

controlled human infection model: vaccinate volunteers and then infect with pathogen

Question 21

Why are we able to do CHIM study with HCV?

Answer 21

because we have highly effective antivirals, cure chronic carriers

Question 22

What is the HCV CHIM Aim?

Answer 22

to asses safety and efficacy of HCV vaccine candidates to prevent chronic HCV infection

Question 23

Why must the reliability of the HCV inoculum be assesed in CHIM study?

Answer 23

• reliability of infectivity
• clinical course
• spontaneous clearnace rate
• curability

Question 24

Describe the morphology of HDV

Answer 24

• env, viroid like
• • circular ssRNA
• subviral agent
• can replicate autonomously
• requires HBV surface proteins for release and uptake

Question 25

What Ags does HBV share with HDV?

Answer 25

S, M, L HBsAgs

Question 26

How do you get infected with HDV?

Answer 26

• co-infection with HBV
• superinfection with HBV (comes into chronic HBV carriers)

Question 27

What is the HDV route of transmisson

Answer 27

same as HBV because it has the same envelope as HBV (includes cell R)