Hepatitis C Virus Flashcards
What is viral hepatitis?
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
What is the spectrum of viral hepatitis?
Wide spread
Asymptomatic, acute, chronic, fulminant (death)
What is acute viral hepatitis?
Mild or severe
Fulminant (A, B, C, D or E)
Usually severe primary, high mortality
Encephalopathy, coagulopathy, multi organ failure
What is chronic hepatitis?
B,C,D and rarely E
Presence of virus for more than 6 months
What are the routes of transmission of viral hepatitis?
Faecal oral
Parenteral- contact with body fluids
What is Hepatitis A virus (HAV)?
Infectious hepatitis
What is Hepatitis B virus (HBV)?
Homologous serum hepatitis
What are the causative agents for Hepatitis A and B
non-A, non-B hepatitis virus
Are all cases of Hepatitis caused by A and B?
No, not many cases caused by A and B
What is transmitted parenterally?
HCV (not via the alimentary tract)
What is known to cause chronic infections?
NANBH
Non A Non B hep Virus
What is most common to occur in Hepatitis C virus?
Cirrohsis and chronic liver disease
What was the experiment to test for Hepatitis C in chimpanzees?
Infection passed experimentally to chimpanzees
Infectious agent passed through 50nm filter
Agent inactivated by solvents
Probably a small, enveloped virus
What is HAV?
Positive
RNA
Picornaviridae
What is Hep B?
Partly ds DNA positive sense RNA
Hepadnaviri dae
What is Hep C?
Partly ds DNA positive sense RNA
Flaviviridae
What is Hep D?
Circular RNA
Deltaviridae
What is Hep E?
Positive sense RNA
Calciviridae
What are the clinical features of acute hep C?
Most asymptomatic
<1% fulminant
What are the clinical features chronic hep C?
50-70%
20% cirrhosis
3-7% HCC
What does HCV account for?
Around 30% liver transplants
How was HCV cloning initially?
It was difficult to characterises due to inability to grow in culture
Eventually cloned in 1989
What is HCV derived from?
Derived from roughly 10kb ssRNA, expressed proteins that react with patient antisera
What family does HCV belong to?
Flavivirus
Why is HCV virion difficult to detect?
Low levels of virus in plasma
What is the morphology the HCV virion?
Roughly 50nm spherical particles
Enveloped
React with antibodies
What is the classification of HCV?
Flavivirus family hepacivirus genus
What is the HCV genome structure?
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
What are structural proteins composition?
Core (C) Envelope glycoproteins (E1, E2), p7 protein
What are non-structural proteins (translated into polyprotein then cleaved by viral proteases)?
Serine protease/helicase/NTPase (NS2/3), RNA-dependent RNA polymerase (NS5b), protease cofactor (NS4a), less well characterised or not known (NS4b, NS5a)
What is the HCV replication cycle?
- Receptor binding (CD81, SRB1, Claudin, Occludin)
- Endocytosis
- Uncoating
- Translation/processing
- RNA replication
- Virion morphogenesis
- Virion transport
- Fusion and release
What is the HCV protein function?
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)
What is the viral family closely related to?
Dengue and yellow fever viruses (flavivirus)
What do isolates of HCV from different sources fall into?
Separate genotypes (1 & 2 a & b, & 3, 4, 5 & 6a)
What are HCV strains characterised by?
DNA sequencing
What is the nucleotide homology between most divergent HCV strains?
65% nucleotide homology
80% between a and b
What new genus has HCV been placed in?
Flaviviruse family called Hepacivirus
What is the prevalence and incidence of falviviridae?
170 m people ww/roughly 3% of the population
How many Americans are chronically infected with falviviridae?
2.7M Americans chronically infected
What age group is typically infected with falviviridae?
Most common in 30-49 years
• Illegal drug use in/around Vietnam war?
What is the differences in falviviridae epidemiology across countries?
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
What are the 6 different HCV genotypes and their distributions?
- Is the most common (46%) and is distributed worldwide. World wars
- Mediterranean countries and the far East
- Europe
- Middle East, Bilharzia treatment
- South Africa
- Hong Kong, Injecting drug user (IDU)
What is the source of HCV infection in the western world?
- Sharing needles and syringes (60%)
- Having sex without condoms with someone who has hepatitis C <5-15% i.e. rare
- Being born to a mother who has hepatitis C <5% i.e. rare
- In past, blood transfusion, blood products
What is the result of Hepatitis C virus infection?
Chronic infection
Ab and cytotoxic T-cell production exacerbates liver inflammation
Liver cirrhosis occurs
Hepatocellular carcinoma (HCC) can eventually occur
How many HCCs are viral?
80%
How many of the HCCs are HBV?
60%
How many of the HCCs are HCV?
40%
What factors promote progression or severity?
Alcohol Age > 40 years at time of infection HIV co-infection Other o Male gender o Chronic HBV co-infection
What is the new Hep C vaccine?
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
What is the prime boost approach of the Hep C vaccine?
Stimulate a T cell response
