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72 Cards in this Set

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What family of virus is HBV?
member of the hepaDNAviridae family.
How is it transmitted?
via blood and other body fluids, and from mother to infant during birth.
What kind of nucleic acid does HBV have?
DNA
Where does HBV replicate? Does it use anything special?
in hepatocytes and uses reverse transcription to replicate its genome.
What kinds of infections does HBV cause?
Infections can be acute, or chronic and last for years.
Epidemiology of HBV?
Over 250 million people are chronically infected
Where is HBV most common?
mostly in Asia and Africa (1.2 million in the U.S., 4000 deaths/yr);
What’s the prognosis for HBV infection?
Out of 1.2 million infected, 4000 deaths/yr in US
25 to 40% of these patients will die from liver cirrhosis or hepatocellular carcinoma (HCC).
How has HBV transmission been greatly decreased?
Used to be called post transfusion hepatitis
Now, monitoring of the blood supply and universal precautions has greatly reduced HBV via transfusion.
What’s the tx for HBV?
None, but there is a safe and effective recombinant vaccine.
What kind of vaccine is used for HBV?
Safe and effective recombinant vaccine
What’s a major complication of HBV infection? Why?
co- or super-infection with Hepatitis D virus (HDV).
HDV genome is replicated in cells in the absence of HBV, but production of infectious HDV virions requires the presence of HBV surface antigen protein (HbsAg).
What’s the prognosis for co-infection of HDV w/ HBV?
may result in a more severe disease than HBV alone, but overall course of infection is similar
What’s more common in HBsAg carrier w/ HDV: coninfection or superinfection? Why?
Superinfection more common and much more serious
Since most of the hepatocytes are already producing HBsAg, HDV can replicate without delay.
Whats the clinical course of superinfection of HBsAg carrier w/ HDV?
Since most of the hepatocytes are already producing HBsAg, HDV can replicate without delay
Within a few weeks, titers of HDV in the blood can approach 1011 virions / ml.
How is superinfection of HBsAg carrier w/ HDV prevented?
Vaccination against HBV prevents infection with HDV.
What other viruses are Patients infected with HBV also at risk for?
similarly transmitted viruses, including HCV and HIV.
What’s the HBV virion called? What kind of structure?
Dane particle, is enveloped.
What’s a Dane particle?
Name of the HBV virion—enveloped and contains 3 virus encoded glycoproteins of which HBsAg is the most prevalent and elicits neutralizing Ab’s
What’s HBsAg? Where is it found?
One of 3 virus-encoded glycoproteins in the HBV envelope--most prevalent and elicits neutralizing antibodies.
How big is the HBV genome?
What kind is it?
How many genes?
It is the smallest DNA human virus genome known (3.2 kb),
partially double-stranded, circular;
4 genes encode multiple proteins.
What encloses the genome of HBV?
icosahedral nucleocapsid or core particle, composed of core antigen (HBcAg). Core particle also contains the viral reverse transcriptase (RT).
What’s the core particle of HBV?
Encloses the genome
Composed of core antigen (HBcAg)
Also contains viral reverse transcriptase
Where is the RT located in HBV virion?
In the core particle (which is composed of core antigen=HBcAg)
What’s HBeAg? What’s it an indicator for?
Protein encoded by HBV that isn’t a part of the virion, but is secreted
important indicator of transmissibility.
What 3 types of virus particles are found in the serum of HBV infected patients?
Dane particles
Small spherical particles
Tubular, filamentous particles
What are Dane particles?
contain core particle with viral genome
infectious,
least numerous of the 3 particles found in serum of HBV infected pts.
What are Small spherical particles?
22 nm diameter,
composed of only HBsAg,
no viral genome, no core,
NOT infectious,
most numerous (103-106-fold excess over Danes, 1012/ml) of 3 particles found in serum of infected pts.
What are tubular, filamentous particles?
22 nm diameter, up to 200 nm long,
composedof only HBsAg,
no viral genome, no core, are NOT infectious,
less numerous than small spherical particles.
One of 3 particles found in serum of HBV infected pts
What is HBsAg? What are its Ab’s called?
core Antigen
HBcAg are named anti HBc or HBcAb
What’s HBeAg? What are its Ab’s called?
secreted from HBV infected cell
antibodies to HBeAg are named anti HBe or HBeAb
What’s important to remember for the replication of HBV?
1.Replication of the partially double-stranded (ds) genome occurs via reverse transcription
of an RNA intermediate molecule.
2. Use RNA intermediate (unique among DNA viruses)
3. Incomplete virions outnumber infectious ones 10,000:1!
Steps of HBV replication of partially ds genome?
1. HBV genome delivered to nucleus; "gap" filled
2. dsDNA converted to covalently-closed, circular (CCC) molecule.
3. CCC= template for tsc of viral mRNAs and viral pregenomic RNAs.
4. In cytoplasm, viral mRNAs are translated; pregenomic RNA is translated into RT (remains bound to RNA)
5. Pregenomic RNA-RT complex packaged into core particles in cytoplasm.
6. In core particle, RT performs 3 enzymatic activities to make genomic DNA from pregenomic RNA.
7. envelope added before 2nd strand DNA synth complete—leaves gap in mostly ds genome
What are the three enzymatic activities of RT in the core particle of HBV to make genomic DNA from pregenomic RNA?
1st, it makes complementary DNA strand using pregenomic RNA molecule as template (RNA-dependent, DNA polymerase activity, aka reverse transcription).
2nd, as RT makes cDNA strand, an RNAse H activity digests the pregenomic RNA molecule.
3rd, the RT makes 2nd DNA strand using the ss of DNA as template (DNA-dependent, DNA polymerase activity)
When is the envelope added during HBV replication? What’s the result?
before 2nd strand DNA synthesis is complete,
leaves a gap in the mostly double-stranded genome.
What’s the CCC molecule? Why is it an important therapeutic target?
Covalently closed circular mol:
Made from ds DNA of HBV in nucleus
Serves as template for tsc of viral mRNA and pregenomic RNAs in cytoplasm
Can persist w/o viral replication
critical target for antiviral strategies aimed at “curing" chronic carriers
What makes HBV unique among DNA viruses?
use of an RNA intermediate
HBV encodes its own reverse transcriptase (RT), a target of anti-virals.
What’s “Unbelievable” about the way HBV is released?
Huge numbers of incomplete virions are assembled and released from infected cells.
These "decoy" particles postulated to saturate HBV-specific Ig.
For each infectious virion, roughly 10,000 noninfectious virions are released!
Where is HBV found?
worldwide with widely varying prevalence.
What’s the reservoir of HBV?
chronic carriers, (0.1%-0.5% of U.S. population, >250 million worldwide).
Humans=only host.
How is HBV transmitted?
via blood and body fluids:
a. Half of infections are sexually transmitted.
b. Neonatal infections are most likely acquired during birth.
c. Every virion is infectious!
How infectious is an HBV virion?
Every virion is infectious!
What is HBV tropic for and how?
hepatotropism due to virus-specific receptors on liver cells
hepatocyte-specific tsc factors that enhance HBV replication.
Is HBV cytopathic to liver cells?
Not directly, much of the pathology in HBV infection is immune mediated (CTL).
How is lifelong immunity to HBV conferred (Ab’s to what)?
results after natural infection and is mediated by antibodies to HBsAg.
What does chronic infection of HBV correlate w/?
increased frequency of developing hepatocellular carcinoma (HCC).
What are the clinical Sx of HBV during acute phase?
vary considerably
most individuals show no obvious clinical signs of disease.
What’s the incubation period of HBV like? Then what?
Long: 45-120 days
Followed by short prodromal phase
Pts frequently experience malaise, lethargy, anorexia, pain in the upper right quadrant.
In some, followed by icteric phase (4-8 weeks),
then convalescent period.
How common is chronic active HBV infection?
occurs in 5-10% of adults infected with HBV, and in 80-90% of neonatal exposures.
What’s important to know before trying to make a lab diagnosis of HBV?
to determine phase of the disease in the patient.
What will almost all patients show by lab dx at primary infection w/ HBV?
Almost all exhibit IgM reactivity to HBcAg at primary infection.
Also look for HBsAg, HBeAg, and elevated liver enzymes: ALT, AST.
Which antibody indicates clearance of HBV?
Anti-HBsAg is the neutralizing antibody which protects against re-infection
appearance indicates clearance of virus and is often preceded by the appearance of anti-HBeAg.
What antibodies will be seen in the HBV “window phase” (b/w acute and chronic)?
HBsAg -, Anti-HBs-, Anti-HBc +
How is chronic HBV infection determined?
if HBsAg is in blood beyond 6 months.
What’s the tx for HBV?
1. None that is 100% effective.
2. α-IFN, lamivudine (a reverse transcriptase inhibitor), adefovir (a nucleoside analogue).
How is HBV prevented?
1. HBV vaccine based on HBsAg : Universal childhood vaccination and personnel at occupational risk.
2. Hepatitis B immune globulin (HBIG) injection soon after exposure may reduce symptoms.
3. For infants delivered from HBV chronic carrier mothers, vaccine and HBIG can prevent infection.
How is HBV prevented in infants delivered from chronic carrier mothers?
Vaccine + HBIG can prevent infection
HBV vaccine
based on HBsAg expressed and purified from yeast:
a. For vaccine purposes, 1 serotype based on HBsAg.
b. x3 injections during a six month period.
c. Universal childhood vaccination and vaccination of personnel at occupational risk.
What’s the structure of HDV (delta virus)?
1. RNA genome enclosed in nucleocapsid composed of one protein, HDAg, and surrounded by envelope of HBsAg from HBV.
2. Viral genome: single-stranded, negative-sense RNA genome; 1.7 kb.
What is necessary for HDV to be infectious?
Only in cells infected w HBV
How does HDV replicate? Which HBV protein is req’d?
1. Infectious HDV only produced in cells infected with HBV
2. Complicated mechanism of replication...
3. HDV requires HBsAg to package virions.
Where does HDV occur? Source?
worldwide with similar distribution as HBV.
Infected humans=the source.
How is HDV transmitted?
same means as HBV: via blood, sexually, and perinatally.
Is HDV directly cytopathic?
In contrast to HBV, HDV is directly cytopathic.
What does Coinfection with HBV allow HDV to do? How does this change the outcome of the dz?
produce infectious HDV virions in HBV-infected cells expressing HBsAg;
the outcome of the disease is not appreciably changed.
How is Superinfection of an HBV carrier with HDV relative to coinfection?
More serious.
Many more cells express HBsAg (pt already infected w/ HBV at time of HDV infection) so HDV spreads more rapidly.
HDV is packaged roughly 1000x more efficiently than HBV.
Increases frequency of chronic infection and development of cirrhosis
Are HDV infections acute or chronic?
can become persistent in chronic HBV carriers.
What is the immunity to HDV?
Not clear if long-term immunity to HDV exists.
How is HDV infection seen clinically?
1. Incubation period of 3 to 7 weeks.
2. Patient complaints are similar to those for HBV when HBV/HDV coinfection occurs.
3. Clinical symptoms usually more severe with HDV superinfection.
How is HDV diagnosed in the lab?
1. Detection of anti HDAg antibodies.
2. Detection of delta antigen.
3. Detection of HDV RNA.
Three things that can be detected by the lab in HDV infection
anti-HDAg Ab’s
Delta Ag
HDV RNA
What’s the treatment for HDV?
1. None that are 100% effective.
2. α-IFN may reduce disease symptoms.
How is HDV Prevented?
HBV vaccination prevents HDV