#15 Hep C specifically Flashcards
Genome of Hep C
family
genome
enveloped or not
Flavivirus;
+ssRNA
Enveloped virions that are associated w/ cellular VLDL = very low density lipoprotein
Hep C (flavivirus) 9 kb genome; \_\_\_\_proteins, invovles proteolytic processing
10
The flaviviruses
Eileen flavin has Hep C Dengue Fever West Nile (all flavi viruses)
Why are there so many quise species to Hep C
error-prone RNA polymerase leads to many quasi-species
LIver damage in Hep C is d/t
Liver damge: d/t immunopath; viral replication induces robust innate immune response
Key timeline for dev and tx of Hep C
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
Key addition to therapy to inhibit Hep C
protease inhibitors
Hep C viral life cycle—Hepatocyte specific (10 to 12 virion/day~~ TONS!)
this is nice for us because
allows us to devo vaccine bc very active replicating
Hep C has RNA replication that is ______mediated translation and proteolytic processing
IRES
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
–ssRNA
packaged and shiped out
Where does the shift from -ssRNA–> back to +ssRNA virions occur
in the membranous web
Hep C has ______ associated replication
membrane associated
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
1 month
2
3
Summary of serologic pattern of HCV
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
Hep C acute infection→ _____recovery and clearance and _____persistant infection→ chronic hepatitis → and then see Liver failure/cirrhosis/hepatocellular carcinoma
15%
85%
Role of HCV core protein in HCC
-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)
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
big picture
= small processed RNAs that regulate other mRNAs in sequence-specific manner
miRNA
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
miRNA-122
Deplition of miR-122 will ____ infection in tissue culture and in infected chimps
impair
_____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
IL28b
HCV genotype ___is more prevelant in US
1
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
Genotype
