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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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