44 Hepadnavirus, Hepatitis D, Subviral entities Flashcards
Hep B virus is enveloped or non-enveloped?
enveloped
What is the name of the hepatitis B surface antigen on the envelope?
HBsAg
What is a hepatitis B virion referred to as?
“Dane particle”, it is especially stable for an enveloped virus and is the infectious virion
T/F- The hepatitis B virus capsid is made of core antigen (HBcAg)
true
T/F- HBeAg is also synthesized by Hep B but is secreted from infected cells and NOT incorporated into virions
true, HBeAg is useful as a diagnostic tool
What type of polymerase does the Hep B inner core contain?
RNA dependent DNA polymerase
What is the structure of the Hep B genome?
circular, partially double stranded DNA
In addition to the Dane particle, noninfectious HBsAg containing particles of various shapes are made in abundance, what is the function of these?
speculated to be immune decoys
Describe the life cycle of Hep B virus
- entry: HBsAg binds receptor and migrates through cytoplasm to nucleus
- viral genome expression occurs in nucleus (mRNA made by cellular RNA pol II, exported from nucleus and translated)
- packaging: polymerase RT makes DNA copy of RNA (this is incomplete tx event, leaves DNA genome partially double stranded)
- Egress: capsid with DNA buds into membrane containing HBsAg and virus is released
What are the two kinds of RNA products made by Hep B virus?
Full-length genomic RNA (gRNA) and shorter mRNAs
What areas of the world have highest Hep B rates?
africa, asia, parts of south america
How is Hep B transmitted?
- blood-borne
- mucocutanous or percutanous exposure to blood or body fluids
- sexual contact
- perinatal (especially africa/asia) and through breast milk
Is the mother to child route of Hep B spread common in the united states?
no
T/F- hepatitis B can present with two forms. An acute infection that is eventually cleared or a chronic infection where the virus persists and replicates for the life of the host?
True
Will antibodies against HBsAg be protective if they are present at the time of infection?
yes, will prevent infection
What type of immune response (cellular or antibody) contributes to liver damage and is responsible for clearing hepatitis B after infection?
cellular immunity
Does hepatitis B have a long or short incubation period before symptoms appear?
long
T/F- acute infection results in symptoms the majority of the time with Hep B
False, only symptomatic 25% of the time
Is fulminant hepatitis common or rare with hepatitis B infection?
rare, but can occur
If you get infected earlier in life (e.g. 1-6 months of age) with Hep B are you more likely to clear the virus than someone who gets infected who is greater than 4 years old?
The older you are when you are infected the better chance you have of clearing the virus and not becoming chronically infected.
If you detect E antigen in addition to S antigen in someone with Hep B, is that bad news?
yes, detection of E antigen confers worse severity/prognosis
Is treatment available for chronic hep B infection?
yes, Pol inhibitors (give when liver enzymes are 2X normal. Interferon alpha was used but is not common anymore.
What are the 3 Pol inhibitors given in chronic Hep B?
- entecavir
- lamivudine
- adefovir
What does entecavir target?
HBV reverse transcriptase
What does Lamivudine target?
HBV and HIV reverse transcriptase
Are individuals vaccinated with Hep B vaccine seropositive?
yes, for anti-HBs antibodies
Why is Hepatitis B virus decreasing?
- dev. of vaccine
2. behavioral changes in groups at high risk of adult infection
What is hepatitis delta virus?
A defective virus or subviral entity that requires Hepatitis B surface antigen to get into cells. It is enveloped with a capsid core of delta antigen and has a circular negative strand RNA genome. It steals the envelope and glycoproteins from Hep B.
Describe the HDV (hepatitis delta virus) life cycle
- entry requires HBsAg
- genome is transcribed and replicated by the host RNA polymerase in the nucleus
- completion of genome synthesis requires enzymatic activity of HDV RNA-ribozyme.
- Assembly occurs by budding of delta cores into membranes containing HBsAg provided by co-infecting HBV
Is HDV common in the USA?
no
HDV is transmitted identical routes to HBV, but what is the most common route in the USA for HDV spread?
IV drug abuse
Can HDV cause disease without HBV infection?
no, cannot replicate without it
HDV and HBV acquired together simultaneously will predominantly lead to what? HDV “superimposed” on an already chronic HBV infection will predominantly lead to what?
- simultaneous: fulminant hepatitis
- HDV superimposed on HBV: chronic hepatitis and cirrhosis
(note that each can also cause the other, but it is less common)
T/F- there is a vaccine for Hep B but no antivirals?
true
Which hepatitis viruses are associated with an elevated cancer risk?
B,C
Which hepatitis viruses are associated with chronic hepatitis?
C,D
Which hepatitis virus is the only one that rarely causes acute jaundice?
C rarely does. all others frequently do.
Which two hepatitis viruses are spread through feces rather than blood/body fluid?
A, E
Which hepatitis virus is only found in developing countries rather than globally?
E
What does TSE stand for?
transmissible spongiform encephalopathy
Is there a treatment for TSE?
no
T/F- TSE elicits a severe adaptive immune response?
False, little to no adaptive immune response
What is the normal form of the protein affected by TSE?
PrPc
What is the mutant form of the protein responsible for TSE?
PrPsc (prion)
What is another example of misfolded proteins causing disease?
alzheimers
Is the rapidity of disease symptoms associated with the dose of PrPsc administered?
yes
Do mice that have their PrP genes knocked out get prion disease?
no, and those with extra copies of the PrP gene are more susceptible to TSE
Name 6 common symptoms of TSE
- loss of motor control (ataxia)
- dementia/cognitive dysfunction
- paralytic wasting
- behavioral abnormalities
- insomnia/sleep disturbance
- death
Does TSE have a short or long incubation period?
VERY long
Are all TSEs species specific or can they be transmitted across species?
can be transmitted to another species
T/F- It is currently thought that PrPsc causes glial cell activation stimulating prolific cytokine production in the brain
True, neurons are particularly sensitive to pro-inflammatory cytokines and may be killed as a result
Of the GENETIC human TSE diseases, which are caused by germ line mutations in the PrP gene and which are caused by somatic mutations in the PrP gene?
- Familial creutzfelt-Jakob Disease (germline)
- Gerstmann-Staussler-Scheinker (germ line)
- Fatal familial insomnia (germ line)
- sporadic CJD (somatic)
- sporadic FFI (somatic)
What are three infectious forms of human TSE and how are they each commonly acquired?
- Kuru (cannibalism)
- Iatrogenic (e.g. CJD) (contaminated surgical equipment/brain grafts/pituitary extract injections)
- new variant CJD (associated with BSE infections in britain)
Is normal PrPc composed of primarily alpha or beta helices?
alpha
Is PrP highly conserved among vertebrates?
yes
What characteristic of PrPsc makes it resistant to many proteases and is responsible for the long lived nature?
aggregation
Describe the “seed hypothesis”
In the presence of aggregates, any newly made PrPsc in the cell will tend to become incorporated in the aggregates. This removes unaggregated PrPsc from the cell where upon more unaggregated PrPsc will be generated by virtue of the PrP equilibrium within the cell.
What is the prediction of the “seed hypothesis”? What did research show?
Aggregates of PrPsc would be more infectious than small forms of PrPsc. Research showed that peak specific infectivity is in aggregates of 14-28 PrP molecules (midsize)
