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Infection and Immunity > Hepatitis C Virus > Flashcards

Hepatitis C Virus Flashcards

1
Q

What is viral hepatitis?

A 
Inflammation of liver
Non-specific symptoms
Malaise, fever, headaches
Anorexia, nausea and vomiting 
Right upper quadrant abdominal pain
Dark urine and clay coloured faeces
Jaundice
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2
Q

What is the spectrum of viral hepatitis?

A

Wide spread

Asymptomatic, acute, chronic, fulminant (death)

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3
Q

What is acute viral hepatitis?

A

Mild or severe
Fulminant (A, B, C, D or E)
Usually severe primary, high mortality
Encephalopathy, coagulopathy, multi organ failure

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4
Q

What is chronic hepatitis?

A

B,C,D and rarely E

Presence of virus for more than 6 months

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5
Q

What are the routes of transmission of viral hepatitis?

A

Faecal oral

Parenteral- contact with body fluids

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6
Q

What is Hepatitis A virus (HAV)?

A

Infectious hepatitis

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7
Q

What is Hepatitis B virus (HBV)?

A

Homologous serum hepatitis

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8
Q

What are the causative agents for Hepatitis A and B

A

non-A, non-B hepatitis virus

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9
Q

Are all cases of Hepatitis caused by A and B?

A

No, not many cases caused by A and B

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10
Q

What is transmitted parenterally?

A

HCV (not via the alimentary tract)

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11
Q

What is known to cause chronic infections?

A

NANBH

Non A Non B hep Virus

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12
Q

What is most common to occur in Hepatitis C virus?

A

Cirrohsis and chronic liver disease

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13
Q

What was the experiment to test for Hepatitis C in chimpanzees?

A

Infection passed experimentally to chimpanzees
Infectious agent passed through 50nm filter
Agent inactivated by solvents
Probably a small, enveloped virus

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14
Q

What is HAV?

A

Positive
RNA
Picornaviridae

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15
Q

What is Hep B?

A

Partly ds DNA positive sense RNA

Hepadnaviri dae

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16
Q

What is Hep C?

A

Partly ds DNA positive sense RNA

Flaviviridae

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17
Q

What is Hep D?

A

Circular RNA

Deltaviridae

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18
Q

What is Hep E?

A

Positive sense RNA

Calciviridae

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19
Q

What are the clinical features of acute hep C?

A

Most asymptomatic

<1% fulminant

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20
Q

What are the clinical features chronic hep C?

A

50-70%
20% cirrhosis
3-7% HCC

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21
Q

What does HCV account for?

A

Around 30% liver transplants

22
Q

How was HCV cloning initially?

A

It was difficult to characterises due to inability to grow in culture
Eventually cloned in 1989

23
Q

What is HCV derived from?

A

Derived from roughly 10kb ssRNA, expressed proteins that react with patient antisera

24
Q

What family does HCV belong to?

A

Flavivirus

25
Q

Why is HCV virion difficult to detect?

A

Low levels of virus in plasma

26
Q

What is the morphology the HCV virion?

A

Roughly 50nm spherical particles
Enveloped
React with antibodies

27
Q

What is the classification of HCV?

A

Flavivirus family hepacivirus genus

28
Q

What is the HCV genome structure?

A

Enveloped RNA genome
Positive sense (same as mRNA)
10Kb genome encodes structural (s) and non structural proteins (NS) flanked by regulatory elements
S- env, core and p7
NS- viral enzymes and cofactors
One large open reading frame translated into a 3010aa polyprotein
Processed/cleaved by viral and cellular proteases

29
Q

What are structural proteins composition?

A 
Core (C)
Envelope glycoproteins (E1, E2), p7 protein
30
Q

What are non-structural proteins (translated into polyprotein then cleaved by viral proteases)?

A

Serine protease/helicase/NTPase (NS2/3), RNA-dependent RNA polymerase (NS5b), protease cofactor (NS4a), less well characterised or not known (NS4b, NS5a)

31
Q

What is the HCV replication cycle?

A
  1. Receptor binding (CD81, SRB1, Claudin, Occludin)
  2. Endocytosis
  3. Uncoating
  4. Translation/processing
  5. RNA replication
  6. Virion morphogenesis
  7. Virion transport
  8. Fusion and release
32
Q

What is the HCV protein function?

A

S
Env- receptor binding
P7- ion channel
Core- maintenance of the genome
NS
Enzymes and cofactors
HCV core protein binds to the p53 promoter
This blocks expression of p53
HCV therefore inhibits the ‘Guardian of the genome’ & allows proliferation of cells with DNA damage
Can lead to Hepatocellular carcinoma (HCC)

33
Q

What is the viral family closely related to?

A

Dengue and yellow fever viruses (flavivirus)

34
Q

What do isolates of HCV from different sources fall into?

A

Separate genotypes (1 & 2 a & b, & 3, 4, 5 & 6a)

35
Q

What are HCV strains characterised by?

A

DNA sequencing

36
Q

What is the nucleotide homology between most divergent HCV strains?

A

65% nucleotide homology

80% between a and b

37
Q

What new genus has HCV been placed in?

A

Flaviviruse family called Hepacivirus

38
Q

What is the prevalence and incidence of falviviridae?

A

170 m people ww/roughly 3% of the population

39
Q

How many Americans are chronically infected with falviviridae?

A

2.7M Americans chronically infected

40
Q

What age group is typically infected with falviviridae?

A

Most common in 30-49 years

• Illegal drug use in/around Vietnam war?

41
Q

What is the differences in falviviridae epidemiology across countries?

A 
Reflects routes of infection and origin
Italy
A disease of the elderly 
Egypt- 15-20% seropositive: Bilharzia treatment with dirty needles
Highest levels in the world
42
Q

What are the 6 different HCV genotypes and their distributions?

A
  1. Is the most common (46%) and is distributed worldwide. World wars
  2. Mediterranean countries and the far East
  3. Europe
  4. Middle East, Bilharzia treatment
  5. South Africa
  6. Hong Kong, Injecting drug user (IDU)
43
Q

What is the source of HCV infection in the western world?

A
  1. Sharing needles and syringes (60%)
  2. Having sex without condoms with someone who has hepatitis C <5-15% i.e. rare
  3. Being born to a mother who has hepatitis C <5% i.e. rare
  4. In past, blood transfusion, blood products
44
Q

What is the result of Hepatitis C virus infection?

A

Chronic infection
Ab and cytotoxic T-cell production exacerbates liver inflammation
Liver cirrhosis occurs
Hepatocellular carcinoma (HCC) can eventually occur

45
Q

How many HCCs are viral?

A

80%

46
Q

How many of the HCCs are HBV?

A

60%

47
Q

How many of the HCCs are HCV?

A

40%

48
Q

What factors promote progression or severity?

A 
Alcohol
Age > 40 years at time of infection
HIV co-infection
Other
o	Male gender
o	Chronic HBV co-infection
49
Q

What is the new Hep C vaccine?

A

Shown promising results in an early clinical trial at Oxford University, generating strong and broad immune responses against the virus causing the disease
The vaccine was found to be very safe and well tolerated in the 15 healthy human volunteers who took part in the phase 1 safety trial
A trial to test the efficacy of the vaccine is now underway among intravenous drug users in two sites in the USA. It is the first hepatitis C vaccine to reach this stage of clinical trials

50
Q

What is the prime boost approach of the Hep C vaccine?

A

Stimulate a T cell response

Infection and Immunity (20 decks)

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