WEEK 3: HEPATITIS C VIRUS

Question 1

HVC belongs to Flaviviridae family tree - what’s that?

Answer 1

a family of positive polarity, single-stranded, enveloped RNA viruses

Question 2

how many pathogens is in the flaviviridae family

Answer 2

69 pathogens - this family is a major global health problem

Question 3

is there an effective vaccine against HVC?

Answer 3

no.

Question 4

why is egypt at the forefront for HCV treatment?

Answer 4

(around 50 years ago) A huge problem occured when schistosomiasis affected many people (a parasite in the Nile that spread to humans via freshwater snails). Mass treatment with repeatedly used contaminated needles rapidly spread HCV.

Question 5

In Egypt, how many jabs were used to treat people with anti-schistosomial therapy?

Answer 5

360,000,000 over 19 years

Question 6

how big is the HCV virus?

Answer 6

50-80nm

Question 7

how does HCV hide itself from neutralising antibodies?

Answer 7

the virus moves onto low-density lipoproteins and makes the lipid bigger

Question 8

what is formed when the HCV virus moves onto the lipoprotein in the body?

Answer 8

it forms a lipoviral particle

Question 9

what cells are infected by HCV?

Answer 9

70% of infections surround liver cells. Hepatocytes, intestinal enterocytes, B lymphocytes, astrocytes (causes neurological damage)

Question 10

how is HCV transmitted?

Answer 10

within host - cell to cell. host to host - contaminated blood transfusion, needle stick injury or drug use

Question 11

how many individuals resolve HCV virus?

Answer 11

20%

Question 12

how many victims of HCV develop cirrhosis?

Answer 12

25% - this is within 20 years

Question 13

what are the symptoms of HCV?

Answer 13

high levels of bilirubin makes the skin yellow, jaundice, ascites (fluid in abdomen), varices (enlarged veins), pruritis (severe itching), lichen planus (rash)

Question 14

What does a positive polarity RNA virus mean?

Answer 14

it gets picked up by a host ribosome and is translated

Question 15

What is the HCV genome flanked by?

Answer 15

on either side by its 5’ untranslated region and a 3’ untranslated region

Question 16

how is HCV genome read?

Answer 16

one continuous open reading frame

Question 17

how many genes are in the genome?

Answer 17

10 genes

Question 18

what are the phosphoprotein inhibitors?

Answer 18

elbasvir, ledipasvir, velpatasvir, pibrentasvir

Question 19

what 3 protein have been used and targeted by the pharmaceutical company successfully?

Answer 19

serine protease, phosphoprotein and RNA dependent RNA polymerase

Question 20

What antibodies are initially looked for?

Answer 20

they look for antibodies that would bind to hep A or hep B. A negative test means they don’t have theses diseases. A pcr test for hep C antibodies is then tested.

Question 21

What is detected after confirmation of HCV?

Answer 21

quantity of the virus using a quantitative PCR

Question 22

if a “naked” HCV virus enters a cell, what cell receptor does it bind to?

Answer 22

Glycosaminoglycans (GAGs)

Question 23

if a “lipidated” HCV virus enters a cell, what cell receptor does it bind to?

Answer 23

low density glycoprotein receptor

Answer 24

endosomes store virons then theya cidiify
librates rna
rna is picked up by host cell ribosomes
akes viral prtoines
in er^^
then some of the rna initally in infected cell must be replicated. positive polarity rna virus must be regulated by a negative intermediate.
NS4b gene producesprotein that produces viral asselbmy web factories. here vireses are made in infected cells.

then exocytosed out o f cell
transort it medaited out of cell where they acquire glycoprotein envelope.

Question 25

what is the half life for free HCV?

Answer 25

2-3 hours, lipoprotein virus is less

Question 26

what is the half life of HCV infected cells?

Answer 26

several days to weeks

Question 27

how high is HCV mutation rate?

Answer 27

very high, 1 in 17000 nucleotides

Question 28

why does HCV have a high mutation rate?

Answer 28

the RNA dependent RNA polymerase is intrinsically error prone

Question 29

what is cirrhosis?

Answer 29

Cirrhosis is scarring (fibrosis) of the liver caused by long-term liver damage. The scar tissue prevents the liver working properly

Question 30

what is hypocholesterolemia?

Answer 30

Hypocholesterolemia is the presence of abnormally low (hypo-) levels of cholesterol in the blood (-emia)

Question 31

why could HCV cause type 2 diabetes?

Answer 31

HCV may increase the body’s insulin resistance

Question 32

what interferons are important for immune control of HCV?

Answer 32

type 1 and 3 IFN

Question 33

what is HCV

Answer 33

Hepatatic C virus

Question 34

how do serine protease inhibitors work?

Answer 34

they block the activity of the active site of the serine protease

Question 35

what are the serine protease inhibitors?

Answer 35

grazoprevir, glecaprovir and voxilaprevir

Question 36

what are the RNA dependent RNA polymerase inhibitors?

Answer 36

sofosbuvir and dasabuvir

Question 37

how is HCV treated?

Answer 37

with inhibitors directed at 3 proteins - MUST be more than one inhibitor drugs used for effective treatment

Question 38

is cirrhosis irreversible?

Answer 38

no

Question 39

what is the unique entry site called that the RNA contains?

Answer 39

IRES - internal ribosome entry site

Question 39

how is RNA of HCV read?

Answer 39

one continuous open reading frame

Question 40

how is the core, E1 and E2 liberated?

Answer 40

by cellular signalase and signal peptide found in the cell

Question 41

what makes envelope glycoproteins?

Answer 41

signallase

Question 42

what does viroporin do?

Answer 42

its important in moving virus complexes through cytoplasm