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Hepatitis B

Hepatitis B virus (HBV) is a member of the Hepadnavirus family and responsible for Hepatitis B, a serious disease that attacks the liver.

Microbiology-
   Virus classification:-
   Group: Group VII (dsDNA-RT)
   Family: Hepadnaviridae
   Genus: Orthohepadnavirus
   Species: Hepatitis B virus

Structure-
   Hepatitis B virus (HBV) is a member of the Hepadnavirus family. The virus is one of the smallest enveloped animal viruses with a virion diameter of 42nm, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core.These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigen (HBsAg), and is produced in excess during the life cycle of the virus.
   The virus particle, (virion) consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein.The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity.The outer envelope contains embedded proteins which are involved in viral binding of, and entry into, susceptible cells.


Genome-
> The genome consists of 3,215 nucleotides. It has compact organization, with four    overlapping reading frames running in one direction and no noncoding regions. There    are four known genes encoded by the genome called C, X, P, and S.
      C - The core protein
      P - The polymerase
      S - The 3 polypeptides of the surface antigen (preS1, preS2 and S - produced from             alternative translation start sites.
      X - A transactivator of viral transcription (and cellular genes?). HBx is conserved in            all mammalian (but not avian) hepadnaviruses. Though not essential in            transfected cells.
> The four overlapping open reading frames (ORFs) in the genome are responsible for    the transcription and expression of seven different hepatitis B proteins.
> The genome of HBV is made of circular DNA, but it is unusual because the DNA is not    fully double-stranded.

Replication-
> The life cycle of Hepatitis B virus is complex.
> Hepatitis B is one of a few known non-retroviral viruses which use reverse    transcription as a part of its replication process.
< In order to reproduce, the hepatitis B virus, must first attach onto a cell which is    capable of supporting its replication.
> The virus gains entry into the cell by binding to a receptor on the surface of the cell    and enters it by endocytosis.
> Because the virus multiplies via RNA made by a host enzyme, the viral genomic DNA    has to be transferred to the cell nucleus by host proteins called chaperones.
> The DNA enters into the nucleus, where it is known to form a convalently closed    circular form called CCC DNA.
> The partially double stranded viral DNA is then made fully double stranded and    transformed into closed circular supercoiled DNA (cccDNA) that serves as a template    for transcription of four viral mRNAs.
> The largest mRNA, (which is longer than the viral genome), is used to make the new    copies of the genome and to make the capsid core protein and the viral DNA    polymerase.
> These four viral transcripts undergo additional processing and go on to form progeny    virions which are released from the cell or returned to the nucleus and re-cycled to    produce even more copies.
> The long mRNA is then transported back to the cytoplasm where the virion P protein    synthesizes DNA via its reverse transcriptase activity.

Life Cycle:
       In order to reproduce, the hepatitis B virus, must first attach onto a cell which is capable of supporting its replication. Although hepatocytes are known to be the most effective cell type for replicating HBV, other types of cells in the human body have be found to be able to support replication to a lesser degree. The initial steps following HBV entry are not clearly defined although it is known that the virion initially attaches to a susceptible hepatocyte through recognition of cell surface receptor that has yet to be indified. The DNA is then enters into the nucleus, where it is known to form a convalently closed circular form called CCC DNA. The (-) strand of such CCC DNA is the template for transcription by cellular RNA polymerase II of a longer-than-genome-length RNA called the pregenome and shorter, subgenomic transcripts, all of which serve as mRNAs. The shorter viral mRNAs are translated by ribosomes attached to the cell's endoplasmic reticulum and the proteins that are destined to become HBV surface antigens in the viral envelope are assembled. The pregenome RNA is translated to produce a polymerase protein, P, which then binds to a specific site at the 3' end of its own transcript, where viral DNA synthesis eventually occurs. Occuring at the same time as capsid formation, the RNA-P protein complex is packaged and reverse transcription begins. At early times after the infection, the DNA is recirculated to the nucleus, where the process is repeated, resulting in the accumulation of 10 to 30 molecules of CCC DNA and an increase in viral mRNA concentrations.


 

 
     
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