Lec 14: Hepadnaviruses (Hep B Virus) Flashcards
Hepadnaviruses: Cause _______ and they have ___ genomes
hepatitis
DNA
Hepadnaviruses Unique characteristics: (2)
- ) have very small genomes, which are used with great economy to encode the virus proteins and to control expression of the virus genes.
- ) their DNA genomes are replicated via an RNA intermediate.
Hepadnaviruses class? =
Class VII
____ ______ people may have been infected with HBV.
~400 million
Over 50 million new HBV infections each year, mostly in
babies who acquire the infection from their mothers.
Many HBV infections result in…
However, the infection in children is…
…mild symptoms or are asymptomatic, especially in children
…most likely to become persistent, 90-95% vs 1-10% in adults.
Individuals who are persistently infected with HBV may…
…remain healthy for much of the time, but some develop severe hepatitis, which may eventually lead to liver cancer
Hepadnaviruses are present in
the blood and semen of infected individuals.
Hepadnaviruses mode of transmission is
similar to that of HIV.
HBV Virion shape =
roughly spherical, with a diameter of 42 nm.
HBV Virion also has
envelope enclosing a capsid, with DNA and P (polymerase) protein inside.
HBV Genome =
Also…
two strands of DNA
…one of which is incomplete; hence the DNA is partly single stranded and partly double-stranded
(HBV Genome)
A short sequence is…
…triple-stranded as a result of a complementary sequence at the 5 ends, and this results in the DNA having a circular conformation.
(HBV Virion)
At the 5’ end of each of the DNA strands there is
…a covalently linked molecule:
- a capped RNA on the short strand and
- a protein (P) on the long strand.
P (polymerase) protein =
a multifunctional protein!
P (polymerase) protein activities: (3)
- ) reverse transcriptase activity
- ) ribonuclease H (RNase H) activity (catalyzes the cleavage of RNA)
- ) DNA-dependent DNA polymerase activity
HBV Capsid: (2)
- icosahedral symmetry, constructed from dimers of the C (core) protein
- Has holes in it and short spikes protrude from its surface
(HBV Envelope) contains…
…3 protein species:
small (S), medium (M) and large (L)
HBV envelope protein species:
The M and L proteins are longer versions of the S protein, which is the most abundant of the three.
In addition to virion, there are
Some are…
particles that are composed of lipid and virus envelope proteins, but do not contain nucleocapsids
…spheres and some are filaments
What vastly outnumber the virions?
the non-infectious particles, especially the spheres,
The reason to have non-infectious particles is
unknown, presumably function as a decoy to survive the host immune system.
In addition to the virions and non-infectious particles…
aka
a soluble virus protein is found in the blood of some infected individuals.
aka hepatitis B e antigen (HBeAg)
function of HBeAg =
not known
HBeAg is widely used as
a target of HBV detection
HBV GENOME IS
highly efficient
Sequencing of many HBV isolates has revealed…
These human viruses are related to…
…8 genetic groups (genotypes A–H)
…similar viruses in other primate species.
The HBV genetic groups are
fairly restricted geographically, e.g. genotype A predominates in Northern Europe while genotypes B and C are in Asia.
Endocytosis of attached HBV virion followed by
release of nucleocapsid and entry into the nucleus
Release of HBV genome from
the capsid and conversion into covalently closed circular DNA (cccDNA)
During DNA synthesis, a nucleocapsid may either: (2)
- ) move to the nucleus where its DNA boosts the pool of virus DNA ( + feedback loop) OR
- ) bud through a membrane containing virus envelope proteins to form a virion
Original HBV vaccines consisted of:
non-infectious spheres and filaments extracted from blood donations from HBV carriers.
New HBV vaccines are produced using:
recombinant yeast cells containing the gene for the S protein.
Vaccination programs have been successful in
reducing the % of HBV carriers in some parts of the world.
Alpha-interferon has been used for some years to
treat HBV-infected persons.
c treatment does not
eliminate the infection, but it results in a significant reduction in viraemia in about 20-30 % of cases.
Alpha-interferon side-effects:
influenza-like symptoms and weight loss
an improvement over α-interferon =
The drug Lamivudine (HIV treatment)
Lamivudine =
target =
a nucleoside analogue, is also used to treat HBV infection
target = P protein
Why Lamivudine is an improvement over α-interferon: (3)
- ) it suppresses virus replication with a low incidence of side-effects, is administered by mouth rather than by injection and is cheaper.
- ) Longterm treatment may lead to lamivudine-resistant HBV mutants.
- ) But the mutants may be treated by other nucleoside analogues such as adefovir.
