From Wikipedia, the free encyclopedia
Hepatitis B virus, abbreviated
HBV, is a species of the genus
Orthohepadnavirus, which is likewise a part of the
Hepadnaviridae family of viruses.
This virus causes the disease hepatitis B.
Main article: Hepatitis B
In addition to causing Hepatitis B, infection with HBV can lead
to cirrhosis and hepatocellular carcinoma.
It has also been suggested that it may increase the risk of pancreatic
The Hepatitis B virus is classified as the type species
of the Orthohepadnavirus, which
contains three other species: the Ground squirrel hepatitis
virus, Woodchuck hepatitis virus, and the Woolly
monkey hepatitis B virus. The genus is classified as part of
the Hepadnaviridae family, which
contains two other genera, the Avihepadnavirus and a second which
has yet to be assigned. This family of viruses have not been
assigned to a viral order. Viruses
similar to Hepatitis B have been found in all the Old World great
apes (orangutan, gibbons, gorillas and chimpanzees) and from a New World woolly monkey
suggesting an ancient origin for this virus in primates.
The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on
antigenic epitopes present
on its envelope proteins, and into eight genotypes (A-H) according
to overall nucleotide sequence variation of the genome. The
genotypes have a distinct geographical distribution and are used in
tracing the evolution and transmission of the virus. Differences
between genotypes affect the disease severity, course and
likelihood of complications, and response to treatment and possibly
A simplified drawing of the HBV particle and surface antigen
Hepatitis B virus (HBV) is a member of the Hepadnavirus
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 similar to retroviruses.
The outer envelope contains embedded proteins which are involved in
viral binding of, and entry into, susceptible cells. The virus is
one of the smallest enveloped animal viruses with a virion diameter
of 42 nm, 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.
It consists of:
Hepatitis D virus requires HBV envelope
particles to become virulent.
The genome organisation of HBV. The genes overlap.
The genome of HBV is made
of circular DNA, but it is unusual
because the DNA is not fully double-stranded. One end of the full
length strand is linked to the viral DNA polymerase. The genome is 3020-3320
nucleotides long (for
the full length strand) and 1700-2800 nucleotides long (for the
short length strand).
The negative-sense, (non-coding), is complementary to the viral
mRNA. The viral DNA is found in the nucleus soon after infection of
the cell. The partially double-stranded DNA is rendered fully
double-stranded by completion of the (+) sense strand and removal
of a protein molecule from the (-) sense strand and a short
sequence of RNA from the (+) sense strand. Non-coding bases are
removed from the ends of the (-)sense strand and the ends are
There are four known genes encoded by the genome called C, X, P,
and S. The core protein is coded for by gene C (HBcAg), and its
start codon is preceded by an upstream in-frame AUG start codon
from which the pre-core protein is produced. HBeAg is produced by
proteolytic processing of the pre-core protein. The DNA polymerase
is encoded by gene P. Gene S is the gene that codes for the surface
antigen (HBsAg). The HBsAg gene is one long open reading frame but
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) are
The function of the protein coded for by gene X is not fully
There are eight known genotypes labeled A through H.
A possible new "I" genotype has been described,
but acceptance of this notation is not universal.
Different genotypes may respond to treatment in different ways.
The genotypes differ by at least 8% of the sequence and have
distinct geographical distributions and this has been associated
with anthropological history. Type F which diverges from the other
genomes by 14% is the most divergent type known. Type A is
prevalent in Europe, Africa and South-east Asia, including the Philippines. Type B and
C are predominant in Asia; type D
is common in the Mediterranean area, the Middle East and India; type E is localized in sub-Saharan Africa;
type F (or H) is restricted to Central and South America. Type G has been found in
France and Germany. Genotypes A, D and F are predominant
in Brazil and all genotypes
occur in the United
States with frequencies dependent on ethnicity.
The E and F strains appear to have originated in aboriginal
populations of Africa and the New World, respectively.
Within genotypes 24 subtypes have been described which differ by
4-8% of the genome.
Type A has two subtypes: Aa (A1) in Africa/Asia and the
Philippines and Ae (A2) in Europe/United States.
Type B has two distinct geographical distributions: Bj/B1 ('j' -
Japan) and Ba/B2 ('a' - Asia). Type Ba has been further subdivided
into four clades (B2 - B4).
Type C has two geographically subtypes: Cs (C1) in South-east
Asia and Ce (C2) in East Asia. The C subtypes have been divided
into five clades (C1 - C5). A sixth clade (C6) has been described
in the Philippines but only in one isolate to date.
Type C1 is associated with Vietnam, Myanmar and Thailand; type C2 with Japan, Korea
and China; type C3 with New Caledonia and
Polynesia; C4 with Australia; and C5 with the
further subtype has been described in Papua, Indonesia.
Type D has been divided into 7 subtypes (D1 - D7).
Type F has been subdivided into 4 subtypes (F1 - F4). F1 has
been further divided in to 1a and 1b. In Venezuela subtypes F1, F2, and F3 are found
in East and West Amerindians. Among South Amerindians only F3 was
found. Subtypes Ia, III, and IV exhibit a restricted geographic
distribution (Central America, the North and the South of South
America respectively) while clades Ib and II are found in all the
Americas except in the Northern South America and North America
Hepatitis B virus 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
- The virus gains entry into the cell by binding to a receptor on
the surface of the cell and enters it by endocytosis. The cell surface receptor has
yet to be identified however it is suspected to be a member of the
ovalbumin family of serine protease inhibitors.
- The virus membrane then fuses with the host cell's membrane
releasing the mRNA and core proteins into the cytoplasm.
- 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 core proteins dissociate from the
partially double stranded viral DNA is then made fully double
stranded and transformed into covalently closed circular DNA
(cccDNA) that serves as a template for transcription of four viral
- 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
- 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
- The long mRNA is then transported back to the cytoplasm where
the virion P protein synthesizes DNA via its reverse transcriptase
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