Medical Microbiology & Immunology
Lecture 26 Virology Hepatitis Viruses I & II
1) To classify the hepatitis viruses.
Hepatitis A Virus (HAV) – Picornaviridae
Hepatitis B Virus (HBV) – Hepadnaviridae
Hepatitis C Virus (HCV) – Flaviviridae
Hepatitis D Virus (HDV) – Unclassified
Hepatitis E Virus (HEV) – Unclassified
2) To identify the morphological structural and genetic differences of the major
hepatitis viruses. See question 3.
3) To describe the replication of hepatitis viruses.
Virus
HAV
Structure
Small, icosahedral, 4 structural
proteins
Genome
(+)ssRNA
HBV
Small (42 nm), circular, smallest
DNA virus, HBcAg (core
antigen), HBeAg (encoded by core
gene), HBsAg (surface antigen) 4 subtypes
Partial
dsDNA
HCV
Core antigen encloses RNA,
envelope E1/E2 surrounds the
core, nonstructural genes encode
protease, polymerase activity,
genetic variability in the envelope.
HBsAg surrounds the RNA
protein complex of HDV, found in
people with hepatitis B virus
infection
(+)ssRNA
six major
genotypes
Spherical 27-34 mm particle,
unenveloped, spikes on surface
(+)ssRNA
HDV
HEV
Circular,
(-)ssRNA
Replication
In the cytoplasm the mRNA is encoded as a
polyprotein that is cleaved into various mature
proteins, assembled, and released by cell lysis.
Incomplete dsDNA is completed by a viral or
host DNA polymerase → transcription by host
RNA polymerase II → mRNA translated to
core, surface, and polymerase proteins → Core
packages RNA and DNA polymerase in the
nucleus → Moves of the cytoplasm where
reverse transcriptase (unique) synthesizes
(-)DNA from (+)RNA → (-)DNA is used to
make a variable short piece of (+)DNA (RNA
degrades) → Virus assembly and release
Replicates through (-) RNA intermediate
Requires the presence of hepatitis B surface
antigen for its transmission and assembly but not
transcription, transcription method not
understood (independent of HBV) replicates in
the nucleus using host factors
4) To discuss the clinical manifestations following infection by hepatitis viruses. See
question 5.
5) To describe the diagnosis, treatment and prevention of hepatitis.
Virus
HAV
HBV
HCV
HDV
HEV
Clinical disease
Fecal oral transmission, shellfish, water. Mostly
asymptomatic.
Acute hepatitis: starts in intestine then moves to liver
causing necrosis, sudden onset after 14-40 day
incubation period fever, poor appetite, nausea,
headache, malaise, vomiting, abdominal pain, and
jaundice with dark urine, clay-colored stool, enlarged
liver. In the is complete.
Acute hepatitis B: similar to hepatitis A, longer
incubation period (average 160 days), slow onset,
transmission through body fluid (blood, saliva,
semen, cervical secretions, blood products)
Chronic hepatitis B: 10-20% of cases become chronic
virus lives and replicates in the liver, HBsAg always
present in serum, cirrhosis of the liver, hepatocellular
carcinoma (200x increased risk)
Transmitted by blood transfusions (no longer), sex
(less than hep B), and needle sharing (40% of cases).
Acute phase is mild, asymptomatic. Results in
chronic disease (85%) leading to cirrhosis of liver
and hepatocellular carcinoma (slow progression 1018 years). Leading cause of liver transplantation US.
Simultaneous delta and hepatitis B infection resulting
in cirrhosis of the liver, superinfection with chronic
hepatitis B (accelerated), permanent hepatitis.
Diagnosis
Clinical picture, radio
immunoassay kits are
available to detect IgM
antibody for HAV.
Treatment and prevention
Prevention: immune serum globulin
administered before or during
incubation period (household
members and travelers going to
endemic areas), inactivated hepatitis
a virus vaccine.
Demonstrate HBsAg in
serum radioimmunoassay,
complement fixation, or
ELISA
Treatment: interferon
Prevention: hyperimmune globulin
(passive), vaccines – HbsAg
synthesized in yeast - 3 doses with
2nd dose 1 month after 1st and 3rd
dose 6 months after 1st
Elevated ALT, ELISA
antibody detection, RIBA
II test confirmation, PCR
detection of RNA
We need a vaccine. Development of
several vaccines are underway
Antibody to Delta
PCR detection
Transmitted through fecal-oral route. Causes acute
disease like HAV. May fulminate especially in
pregnant women. Most cases in India rarely US.
Immunological assays
Presence of specific IgM
PCR Detection of RNA
The surface protein of HDV is
HBsAg and many measures aimed at
limiting the transmission of HBV
will prevent HDV transmission.
No treatment is available
Not known if immune serum
globulin prevents infection