Lec 14: Hepadnaviruses (Hep B Virus)

Question 1

Hepadnaviruses: Cause _______ and they have ___ genomes

Answer 1

hepatitis

DNA

Question 2

Hepadnaviruses Unique characteristics: (2)

Answer 2

1. ) have very small genomes, which are used with great economy to encode the virus proteins and to control expression of the virus genes.
2. ) their DNA genomes are replicated via an RNA intermediate.

Question 3

Hepadnaviruses class? =

Answer 3

Class VII

Question 4

____ ______ people may have been infected with HBV.

Answer 4

~400 million

Question 5

Over 50 million new HBV infections each year, mostly in

Answer 5

babies who acquire the infection from their mothers.

Question 6

Many HBV infections result in…

However, the infection in children is…

Answer 6

…mild symptoms or are asymptomatic, especially in children

…most likely to become persistent, 90-95% vs 1-10% in adults.

Question 7

Individuals who are persistently infected with HBV may…

Answer 7

…remain healthy for much of the time, but some develop severe hepatitis, which may eventually lead to liver cancer

Question 8

Hepadnaviruses are present in

Answer 8

the blood and semen of infected individuals.

Question 9

Hepadnaviruses mode of transmission is

Answer 9

similar to that of HIV.

Question 10

HBV Virion shape =

Answer 10

roughly spherical, with a diameter of 42 nm.

Question 11

HBV Virion also has

Answer 11

envelope enclosing a capsid, with DNA and P (polymerase) protein inside.

Question 12

HBV Genome =

Also…

Answer 12

two strands of DNA

…one of which is incomplete; hence the DNA is partly single stranded and partly double-stranded

Question 13

(HBV Genome)

A short sequence is…

Answer 13

…triple-stranded as a result of a complementary sequence at the 5 ends, and this results in the DNA having a circular conformation.

Question 14

(HBV Virion)

At the 5’ end of each of the DNA strands there is

Answer 14

…a covalently linked molecule:

• a capped RNA on the short strand and
• a protein (P) on the long strand.

Question 15

P (polymerase) protein =

Answer 15

a multifunctional protein!

Question 16

P (polymerase) protein activities: (3)

Answer 16

1. ) reverse transcriptase activity
2. ) ribonuclease H (RNase H) activity (catalyzes the cleavage of RNA)
3. ) DNA-dependent DNA polymerase activity

Question 17

HBV Capsid: (2)

Answer 17

• icosahedral symmetry, constructed from dimers of the C (core) protein
• Has holes in it and short spikes protrude from its surface

Question 18

(HBV Envelope) contains…

Answer 18

…3 protein species:

small (S), medium (M) and large (L)

Question 19

HBV envelope protein species:

Answer 19

The M and L proteins are longer versions of the S protein, which is the most abundant of the three.

Question 20

In addition to virion, there are

Some are…

Answer 20

particles that are composed of lipid and virus envelope proteins, but do not contain nucleocapsids
…spheres and some are filaments

Question 21

What vastly outnumber the virions?

Answer 21

the non-infectious particles, especially the spheres,

Question 22

The reason to have non-infectious particles is

Answer 22

unknown, presumably function as a decoy to survive the host immune system.

Question 23

In addition to the virions and non-infectious particles…

aka

Answer 23

a soluble virus protein is found in the blood of some infected individuals.
aka hepatitis B e antigen (HBeAg)

Question 24

function of HBeAg =

Answer 24

not known

Question 25

HBeAg is widely used as

Answer 25

a target of HBV detection

Question 26

HBV GENOME IS

Answer 26

highly efficient

Question 27

Sequencing of many HBV isolates has revealed…

These human viruses are related to…

Answer 27

…8 genetic groups (genotypes A–H)

…similar viruses in other primate species.

Question 28

The HBV genetic groups are

Answer 28

fairly restricted geographically, e.g. genotype A predominates in Northern Europe while genotypes B and C are in Asia.

Question 29

Endocytosis of attached HBV virion followed by

Answer 29

release of nucleocapsid and entry into the nucleus

Question 30

Release of HBV genome from

Answer 30

the capsid and conversion into covalently closed circular DNA (cccDNA)

Question 31

During DNA synthesis, a nucleocapsid may either: (2)

Answer 31

1. ) move to the nucleus where its DNA boosts the pool of virus DNA ( + feedback loop) OR
2. ) bud through a membrane containing virus envelope proteins to form a virion

Question 32

Original HBV vaccines consisted of:

Answer 32

non-infectious spheres and filaments extracted from blood donations from HBV carriers.

Question 33

New HBV vaccines are produced using:

Answer 33

recombinant yeast cells containing the gene for the S protein.

Question 34

Vaccination programs have been successful in

Answer 34

reducing the % of HBV carriers in some parts of the world.

Question 35

Alpha-interferon has been used for some years to

Answer 35

treat HBV-infected persons.

Question 36

c treatment does not

Answer 36

eliminate the infection, but it results in a significant reduction in viraemia in about 20-30 % of cases.

Question 37

Alpha-interferon side-effects:

Answer 37

influenza-like symptoms and weight loss

Question 38

an improvement over α-interferon =

Answer 38

The drug Lamivudine (HIV treatment)

Question 39

Lamivudine =

target =

Answer 39

a nucleoside analogue, is also used to treat HBV infection

target = P protein

Question 40

Why Lamivudine is an improvement over α-interferon: (3)

Answer 40

1. ) it suppresses virus replication with a low incidence of side-effects, is administered by mouth rather than by injection and is cheaper.
2. ) Longterm treatment may lead to lamivudine-resistant HBV mutants.
3. ) But the mutants may be treated by other nucleoside analogues such as adefovir.