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The Hepatitis B virus is an enveloped double-stranded DNA virus that is part of the Hepadnaviridae family. It is the smallest DNA virus known with a 3200 base pair genome. The virus is somewhat unusual in that the two strands of DNA are not exactly the same. Instead, the minus strand of the virus is almost a complete circle which contains the information to encode the structural proteins of the virus, as well as the replicative proteins. The second strand of the virus, the plus strand, overlaps with most of the minus strand, but it is shorter and tends to vary in length.
There are four known genes encoded by the genome: C, X, P, and
the gene that codes for the surface antigen (HBsAg). The HBsAg
gene is one long open reading frame that contains three in frame
"start" (ATG) codons that divide the gene into three
sections, pre-S1, pre-S2, and S. Because of the multiple start
codons, polypeptides of three different sizes called large, middle,
and small (pre-S1 + pre-S2 + S, pre-S2 + S, or S) can all be produced
by the same gene. The envelope of the 42 nm infectious viral particle,
called the Dane particle, contains all three proteins on its surface
with a predominance of the S protein. 19,
23, www.hepnet.com.
Notice how the surface of the virion contains three different types of proteins. These structrual polypeptides correspond to the small, medium, and large gene products mentioned above. image taken from CDC. "The Pink Book" -- Epidemiology and Prevention of Vaccine-Preventable Diseases, 1999. www.cdc.gov
A schematic of the HBsAg gene.
Notice how the position of the three start codons (ATG) allow for the possibility of three different surface polypeptides.
image created by Neil Wimmer Once it invades the body, the virus binds to the cell surface and penetrates it with the help of its envelope proteins. Inside the plasma membrane of the cell, the virus is not degraded but is transported to the nucleus where the partially circular DNA is made into covalently closed circular DNA (cccDNA). cccDNA functions as the template for RNA synthesis. This RNA is then reverse transcribed into an open, circular DNA molecule. The new, circular DNA is subsequently packaged into viral envelopes in the endoplasmic reticulum and then transported out of the cell. Unlike other viruses, HBV does not integrate itself onto the host genome but retains a core of cccDNA in the nucleus of the cell by transporting some of the newly synthesized HBV DNA back to the nucleus. Thus the HBV continues to replicate itself inside the host's liver cells. 19, 23.
A schematic of the viral lifecycle.
image taken from Mahoney and Kane, 1999. 19. In terms of the HBV vaccine, the most important part of the genome is the HBsAg gene. It is particularly important because the S protein product contains an epitope that generates a protective immune response against the virus, and is thus key in the current HBV vaccine (see Vaccine page).
The particular surface antigen that is important in generating the protective immune response is known as HbsAg, or Hepatitis B surface antigen. This antigen is found on the surface of the viral envelope as well as in excess in the blood. In this latter case, it is in the form of 22nm spherical and tubular particles . It is this protein that can be identified in the serum, and its presence for more than 6 months indicates a chronic HBV infection.
Secondary Structure of the HBsAG Image obtained from Mahoney and Kane, 1999. 19. Notice the two seperate external epitopes that can be recognized by protective immunoglobulin. In the above diagram, they are shown in brackets and labeled, "B cells."
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