Glossary of HBV and HDV

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What is the structure of the HBV genome? How many ORF's does it have?
*partially dsDNA
*4 overlapping ORF's
What constitutes the HBcAg? What do antibodies against this antigen mean?
*the HBcAg, or core antigen, comes from the capsid of the virus
*anti-HBcAg are not protective and do not confer immunity
Where does HBeAg come from? What does its presence in the blood signify? How are antibodies against this antigen interpreted?
*HBeAg is a soluble component of the viral core
*presence of HBeAg means active disease and high infectivity
*presence of anti-HBeAg is a good clinical sign
Where does HBsAg come from? What does its presence mean? What do antibodies against this antigen confer?
*HBsAg comes from the viral envelope and associated proteins
*HBsAg means there is live virus and infection
*anti-HBsAg means resolution and complete immunity
Decsribe the replication of HBV.
The viral DNA is filled in to yield a cccDNA which exists in the host nucleus. cccDNA is transcribed by host RNA pol. The RNA transcript leaves the nucleus and is packaged in a capsid. The viral RT converts the RNA transcript into a pdsDNA genome inside of the capsid.
What is the difference between a Dane particle and an Australia antigen?
The Dane particle is the complete virion whereas the Australia antigen is the empty envelope.
Chronic HBV can pass through several stages, culminating in PHC...what are these stages? How long can the transition from acute infection to PHC take?
*chronic persistent hepatitis
*chronic active hepatitis
*30 years
How are arthritis and glomerulonephritis associated with HBV infection?
HBV infection can lead to the formation of antigen-antibody complexes whose deposition causes these conditions.
Why doesn't infection with HBV overstress the host cell?
The virus regulates its own activity and replication to prevent overstressing the host cell.
A primary infection of HBV has three outcomes - what are they?
1.Acute episode induces a strong immune response which clears the infection and bestows immunity.
2.Acute episode induces an intermediate immune response that fails to clear the infection; persistent infection and chronic state
3.No acute episode and immunotolerance; persistent infection and chronic state
Why do immunosupressed individuals often have an asymptomatic presentation of HBV?
Much of the pathology is associated with CMI and CTL's. These patients have inactive immune system thus little pathology is seen.
Why might a patient show immunotolerance and fail to have an acute episode during initial infection with HBV?
Anergic CTL's.
Integration of viral and tumor DNA is required for the conversion of chronic HBV to PHC.
False: though HBV DNA is often found integrated into tumor DNA this is not required for development of PHC.
HBV infection can spread to extrahepatic tissues - what are three such tissues?
*bile duct epithelia
How is HBV transmitted?
*in blood and body fluids
What do the presence of IgM anti-HBcAg and IgG anti-HBcAg signify?
IgM anti-HBcAg is indicative of a new infection whereas IgG anti-HBcAg is indicative of an old infection.
What is the "window state" that is sometime seen with the serology of patients with acute/non-chronic HBV infection?
The point of the infection where HBsAg has disappeared from circulation but anti-HBsAg has not yet appeared, thus serology will be negative.
When do anti-HBcAg appear in the disease course of HBV?
The appearance of anti-HBcAg is concurrent with the appearance of symptoms.
Describe the antigen/antibody profile of a patient with chronic HBV.
*an initial sharp rise then plateau in HBsAg and HBeAg
*there is a sharp rise then decline of IgM anti-HBcAg with an associated rise in IgG anti-HBcAg
*there is a rise in anti-HBeAg several years after the initial infection
What is the HBV vaccine? Who should receive it?
The vaccine is a recombinant HBsAg. It should be given to all newborns and workers with occupational risk. Also it is effective in the post-exposure setting if given within one week.
Name three compounds used in the treatment of HBV.
2.Interferon alpha
What is the mechanism of action of lamivudine? What problems have been associated with its use?
Lamuvidine (3TC) is an analog of cytosine that when tri-phosphorylated will act as a chain terminator and inhibit DNA synthesis by the viral RT. Many patients experience post-treatment rebound of viremia; also there is emergining resistance to the drug.
What is the mechanism of action of Adefovir?
It is an analog of dAMP which acts as a chain terminator to inhibit DNA synthesis by the viral RT.
What is an absolute condition of infection with HDV?
It can only infect host cells concurrently infected by HBV.
What is the genome structure of HDV? How many ORF's does it encode?
*a small, circular (-) ssRNA
*it has a single ORF
What makes HDV unique among (-) RNA viruses?
It does not code for its own RNA-dependent RNA pol, and seems instead to be transcribed by the host DNA-dependent RNA pol II.
From where does the HDV get its viral envelope lipoproteins?
It parasitizes them from HBV.
How does co-infection with HDV and HBV affect a patient's prognosis?
This combination is associated with a more aggressive clinical course and higher mortality.
What are the two types of infection setting seen with HDV?
*a patient acquires HBV and HDV at the same time
*a HBV patient acquires HDV as a superinfection
How does a patient's ability to clear HBV affect their ability to deal with HDV?
Ability to clear HBV is correlated with ability to clear HDV as well.
How is HDV diagnosed?
Detection of HDV antigen or antibody against HDV antigen.
Is there a vaccine for HDV?
There is not a specific vaccine, but vaccination for HBV confers immunity against HDV.
Are drugs used to treat HBV effective at treating HDV?
No - these drugs affect the HBV RT but not the synthesis of HBs antigen. Thus they are ineffective against HDV.

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