AOBase: Antisense Oligonucleotide Database

the Genome of HBV

It carries a small 3.2 kb circular, partially double stranded DNA genome......

The viral envelope encoded by the S gene contains three distinct configurations synthesized in all persons, termed the large, middle, and major proteins, which are produced by beginning transcription with, respectively, preS1, preS2, or the S gene alone. The preS1 and preS2 represent two of the more immunogenic portions of HBsAg. Several specific antigenic determinants, including the a determinant, common to all HBsAg, and the d, y, w, and r determinants, are mainly of epidemiologic importance. The development of cellular and humoral immunity to HBsAg is protective, and recombinant HBsAg provides the basis for the HBV vaccines currently available. HBsAg :surface (coat) protein produced in excess as small spheres and tubules.

The long P gene encodes the DNA polymerase, which also serves a reverse-transcriptase function, since replication requires RNA intermediates. The X gene encodes two proteins that serve as transcriptional transactivators, aiding viral replication. These proteins may also play a part in the development of hepatocellular carcinoma. Several additional enhancer and promoter elements have also been identified within the HBV genome.

Hepatitis B core antigen (HBcAg) is the nucleocapsid that encloses the viral DNA. When HBcAg-derived peptides are expressed on the surface of hepatocytes, they induce a cellular immune response that is crucial for killing infected cells.

Hepatitis B e antigen (HBeAg), a circulating peptide derived from the core gene and then modified and exported from liver cells, serves as a marker of active viral replication. HBeAg may act as a tolerogen, since its presence in the circulation has been associated with a diminished immune response because of its close resemblance to HBcAg, the putative target of the immune response. With few exceptions, HBeAg is present only in persons who have circulating serum HBV DNA. HBeAg is the diversionary protein diverting the host immune response away from hepatocytes infected with HBV (HBcAg) and allows the virus to replicate unopposed.

Hepatitis B x antigen (HBxAg) is conserved among mammalian hepadnaviruses and the X protein, pX, is essential for viral propagation at least in the woodchuck. During the last decade, efforts have centered on elucidating the oncogenic role of pX in hepatitis B virus infection. The accumulating knowledge on pX indicates that it is a multifunctional regulatory protein which modulates many host functions by communicating directly or indirectly with a variety of host targets as is the case for many viral regulatory proteins, such as T antigens, E1A, and human T cell lymphotropic virus tax. pX, which modulates the transcription machinery and/or modulation protein kinase signaling cascades, transactivates many host genes involved in cell proliferation, cytokine networks, acute immune response, and house-keeping functions. Distinct from the transactivation, pX also modulates DNA repair processes by interacting with p53 and/or repair enzymes which may accumulate mutations and sensitize cells to genotoxic stimuli. Several X-interaction host proteins remain to be characterized as targets of pX. The biological roles of pX have been addressed in various systems in addition to the role of pX on viral reproduction. pX may affect cell cycle progress, response to apoptotic stimuli, cell transformation, and carcinogenesis in the presence or absence of additional oncogenic factors. These biological roles of pX have not been described in terms of pX functions and targets and remain subjects of future research using improved experimental systems and technologies. Such efforts will identify important function(s) of pX for hepatocarcinogenesis.

The whole virion, or Dane particle, is 42nm in diameter and possesses an isometric nucleocapsid or "core" of 27nm in diameter, surrounded by an outer coat approximately 4nm thick. The protein of the virion coat is termed "surface antigen" or HBsAg. It is sometimes extended as a tubular tail on one side of the virus particle. The surface antigen is generally produced in vast excess, and is found in the blood of infected individuals in the form of filamentous and spherical particles. Filamentous particles are identical to the virion "tails" - they vary in length and have a mean diameter of about 22nm. They sometimes display regular, non-helical transverse striations.

1.William M. Lee, M.D.Hepatitis. B Virus Infection .N Engl J Med 1997;Volume 337:1733-1745
2.Mutchnick MG. Acute and chronic hepatitis B. In: Feldman M, Maddrey WC, eds. The liver. Philadelphia: Current Medicine, 1996:4.1-4.24
3. Magnius LO, Espmark JA. New specificities in Australia antigen positive sera distinct from the Le Bouvier determinants. J Immunol 1972;109:1017-1021
4.Seishi Murakami. Hepatitis B Virus X Protein: Structure, Function and Biology. Intervirology 1999;42:81-99
5.Milich DR, Chen MK, Hughes JL, Jones JE.HBeAg is a Diversionary Protein. J Immunol 1998; Feb 15;160(4):2013-21.