#15 Hep C specifically

Question 1

Genome of Hep C
family
genome
enveloped or not

Answer 1

Flavivirus;
+ssRNA
Enveloped virions that are associated w/ cellular VLDL = very low density lipoprotein

Question 2

Hep C (flavivirus) 9 kb genome; 
\_\_\_\_proteins, invovles proteolytic processing

Answer 2

10

Question 3

The flaviviruses

Answer 3

Eileen flavin has
Hep C
Dengue Fever
West Nile
(all flavi viruses)

Question 4

Why are there so many quise species to Hep C

Answer 4

error-prone RNA polymerase leads to many quasi-species

Question 5

LIver damage in Hep C is d/t

Answer 5

Liver damge: d/t immunopath; viral replication induces robust innate immune response

Question 6

Key timeline for dev and tx of Hep C

Answer 6

a. identified in 89 and then
by 98 we have INFα and rivavirin combo therapy
b. by 2004 we see therapy that uses HCV protease inhibitors and people don’t have virus anymore

Question 7

Key addition to therapy to inhibit Hep C

Answer 7

protease inhibitors

Question 8

Hep C viral life cycle—Hepatocyte specific (10 to 12 virion/day~~ TONS!)
this is nice for us because

Answer 8

allows us to devo vaccine bc very active replicating

Question 9

Hep C has RNA replication that is ______mediated translation and proteolytic processing

Answer 9

IRES

Question 10

Hep C will entery→ uncoats→ as +RNA with IRES mediated translation and proteolytic processing →now we are________ that will rearrange in intracell membranous web → back to lots of +ssRNA to be

Answer 10

–ssRNA

packaged and shiped out

Question 11

Where does the shift from -ssRNA–> back to +ssRNA virions occur

Answer 11

in the membranous web

Question 12

Hep C has ______ associated replication

Answer 12

membrane associated

Question 13

Serologic Pattern of Acute HCV infection with progression to chronic infection
_______ after exposure see HCV rNA and for 1- 6 months + for symptoms
ALT levels peak at _____ months
anti HCV rise at _____months and peak at one year and stay that way

Answer 13

1 month
2
3

Question 14

Summary of serologic pattern of HCV

Answer 14

see rise in HCV RNA at one month + symptoms (stays that way 1-6 months)
ALT peaks at 2 months
antiHCV antiB rise at 3 moths and stay high

Question 15

Hep C acute infection→ _____recovery and clearance and _____persistant infection→ chronic hepatitis → and then see Liver failure/cirrhosis/hepatocellular carcinoma

Answer 15

15%

85%

Question 16

Role of HCV core protein in HCC

Answer 16

-will signal transduction paths involved in proilferation
-induce steatosis (lipid accumulation) leading to fatty acid spiral in liver steatosis to incrase oxidative stress
regulates many cellular tumor suppresosr (like p53 and Rb)

Question 17

overal focus on the fact that HCV has proteins that cause steatosis, suppress p53, inhibit NK, activate cell proliferation and induce cell grwoth and preven apoptosis

Answer 17

big picture

Question 18

= small processed RNAs that regulate other mRNAs in sequence-specific manner

Answer 18

miRNA

Question 19

b. ______ is most abundant mRNA in the liver and binds to 2 sites in the 5’ UTR (untranslated region) of HCV genome—enhances translation and/or replication

Answer 19

miRNA-122

Question 20

Deplition of miR-122 will ____ infection in tissue culture and in infected chimps

Answer 20

impair

Question 21

_____gene that encodes antiviral cytokine IFN-γ and that a polymorph w/in IL28B whas strong impact on devo of chronic infection and responsiveness ot IFN therapy
–has implicaitons for HCV therapy to provide insight into HCV host interactions

Answer 21

IL28b

Question 22

HCV genotype ___is more prevelant in US

Answer 22

1

Question 23

Response to IFN +Ribavirin is Dependent on ____
(SVR = sustained virological response)
those with genontype non-1 responded best while those with genotype 1 didn’t respond as well

Answer 23

Genotype