8..hepatitis b viruses 2003Presentation Transcript
Hepatitis B virus (HBV) causes Hepatitis B.
It belongs to the Hepadnavirus family of DNA viruses.
It has an enveloped, icosahedral nucleocapsid core
containing a partially DS circular DNA genome.
The incomplete strand is the plus strand and is associated
with a viral DNA polymerase that functions as both a DNA
dependent-DNA polymerase and RNA-dependent reverse
transcriptase. This polymerase can repair the gap in the
plus strand and render the genome fully double-stranded.
The envelope contains a protein called Surface Antigen
(HBsAg) that is important for lab diagnosis and
The viral genome contains 4 genes: S-gene; C-gene; P-
gene and the X-gene.
S-gene codes for the surface antigen.
C-gene codes for the core antigen (HBcAg) and the eantigen (HBeAg).
P-gene codes for the polymerase.
X-gene codes for the X-protein, which is an activator
of viral RNA transcription.
The core antigen (HBcAg) forms the nucleocapsid
core of the virion and the e-antigen (HBeAg)is the
transmissibility factor secreted from the infected cells
into the blood.
HBV is the only human virus that produces three
different particles that of many spheres (22 nm) and
filaments (22nm wide) along with the virions (42nm)
as seen in the electron microscopy of a patients
HBV has one serotype based on HBsAg for vaccine
purposes and induction of immune response.
The specificity of HBV for liver cells is due to the
virus specific receptors on the hepatocyte cell
membrane (facilitating their entry) and transcription
factors found only in the hepatocyte that enhance
viral mRNA synthesis.
Human only hosts of HBV.
Replication of HBV:
After entry of the virus and its uncoating, the virion DNA polymerase synthesizes the
missing portion of DNA and a double stranded closed circular DNA is formed in the
This DNA serves as a template for mRNA synthesis using the cellular RNA polymerase.
After individual mRNA’s coding for specific proteins are made, a full length transcript of
the positive strand (RNA) is generated.
This full length transcript of RNA generated serves as a template for the minus strand of
progeny DNA using RNA-dependent DNA polymerase or reverse transcriptase (inside
This minus strand of DNA now serves as a template for the plus strand of the genome
DNA, using DNA polymerase.
The RNA dependent DNA synthesis takes place within the newly assembled virion core
in the cytoplasm.
Hepadna viruses are the only viruses that produce
genome DNA by reverse transcriptase with mRNA as
The virion polymerase plays both the roles of RNA
dependent reverse transcriptase and DNA-dependent
Some of the progeny DNA integrates into the host
cell genome and this maintains the carrier state.
Progeny HBV with its HBsAg coating envelope
releases from the cell by budding through the cell
Transmission is via blood, during sexual intercourse
and during childbirth from mother to the newborn.
Only very small amounts of blood necessary for
transmission as evidenced by transmission through
A high incidence of hepatocellular carcinoma
associated with HBV infection indicates that HBV
may well be a human tumor virus. Also immunization
against HBV reduced the incidence of hepatoma in
Pathogenesis includes the virus infecting the hepatocytes
after entering the blood stream and the viral antigens
subsequently displayed on the surface of the cells elicit a
Cytotoxic T-cell mediated immune attack resulting in
inflammation and necrosis. The pathogenesis of HBV is
probably due to the result of this cell-mediated immunity
injury. HBV itself does not cause any CPE.
It is these antigen-antibody complexes that cause some of
the early symptoms such as arthralgias, arthritis and
urticaria and some later complications of chronic
hepatitis such as glomerulonephritis, cryoglobulinemia
5% of patients become chronic carriers defined as HBsAg
persisting in their blood for at least 6 months.
A high rate of hepatocellular carcinomas seen in chronic
Please note that the HBV does not have an oncogene and
as such the carcinoma appears to be the result of
persistent cellular regeneration that attempts to replace
the dead hepatocytes during HBV infection. It could also
be due to insertional mutagenesis when the HBV genome
integrates into the hepatocyte DNA.
Life long immunity mediated by the humoral antibodies
against the HBsAg.
Many HBV infections are asymptomatic and detected only
by the presence of anti-HBsAg.
Incubation period is of 10-12 weeks and symptoms similar
to Hepatitis A.
However, HBV infections are more severe and lifethreatening as well. It may lead to cirrhosis and death.
In cases of HBV and HIV infections together, HBV should
be treated first as Immune reconstitution after HIV
treatment may result in increased damage to hepatocytes
due to the reconstituted Cytotoxic T-cells.
Immunoassay available for detecting HBsAg.
HBcAg test to detect antibodies is not readily
available, especially helpful during the window phase
(after the disappearance of HBsAg and the
appearance of anti-HBsAg in the blood).
HBeAg indicates a high likelihood of transmissibility.
Typically no anti-viral therapy is used in acute hepatitis B.
In chronic cases, a combination of peginterferon alfa-2a or
perinterferon alfa-2b along with/or a nucleoside analogue
such as Lamivudine, Adefovir, Entecavir or telbivudine
that inhibits the reverse transcriptase of HBV.
A combination of tenofovir and emtricitabine can also be
used. Nucleoside analogues are better tolerated than
These drugs reduce hepatic inflammation and lower the
viral load in chronic state and do not cure the infection.
Replication starts once the drug is stopped.
Prevention by a recombinant vaccine of HBsAg
produced in yeasts. Highly effective in prevention.
Hepatitis B immune globulin (HBIG) containing a
high titer of anti-HBsAg for individuals exposed to
All blood for transfusion to be screened for HBsAg.