Lec 14: Hepadnaviruses (Hep B Virus) Flashcards

1
Q

Hepadnaviruses: Cause _______ and they have ___ genomes

A

hepatitis

DNA

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2
Q

Hepadnaviruses Unique characteristics: (2)

A
  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.
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3
Q

Hepadnaviruses class? =

A

Class VII

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4
Q

____ ______ people may have been infected with HBV.

A

~400 million

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5
Q

Over 50 million new HBV infections each year, mostly in

A

babies who acquire the infection from their mothers.

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6
Q

Many HBV infections result in…

However, the infection in children is…

A

…mild symptoms or are asymptomatic, especially in children

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

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7
Q

Individuals who are persistently infected with HBV may…

A

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

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8
Q

Hepadnaviruses are present in

A

the blood and semen of infected individuals.

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9
Q

Hepadnaviruses mode of transmission is

A

similar to that of HIV.

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10
Q

HBV Virion shape =

A

roughly spherical, with a diameter of 42 nm.

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11
Q

HBV Virion also has

A

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

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12
Q

HBV Genome =

Also…

A

two strands of DNA

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

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13
Q

(HBV Genome)

A short sequence is…

A

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

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14
Q

(HBV Virion)

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

A

…a covalently linked molecule:

  • a capped RNA on the short strand and
  • a protein (P) on the long strand.
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15
Q

P (polymerase) protein =

A

a multifunctional protein!

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16
Q

P (polymerase) protein activities: (3)

A
  1. ) reverse transcriptase activity
  2. ) ribonuclease H (RNase H) activity (catalyzes the cleavage of RNA)
  3. ) DNA-dependent DNA polymerase activity
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17
Q

HBV Capsid: (2)

A
  • icosahedral symmetry, constructed from dimers of the C (core) protein
  • Has holes in it and short spikes protrude from its surface
18
Q

(HBV Envelope) contains…

A

…3 protein species:

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

19
Q

HBV envelope protein species:

A

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

20
Q

In addition to virion, there are

Some are…

A

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

21
Q

What vastly outnumber the virions?

A

the non-infectious particles, especially the spheres,

22
Q

The reason to have non-infectious particles is

A

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

23
Q

In addition to the virions and non-infectious particles…

aka

A

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

24
Q

function of HBeAg =

A

not known

25
Q

HBeAg is widely used as

A

a target of HBV detection

26
Q

HBV GENOME IS

A

highly efficient

27
Q

Sequencing of many HBV isolates has revealed…

These human viruses are related to…

A

…8 genetic groups (genotypes A–H)

…similar viruses in other primate species.

28
Q

The HBV genetic groups are

A

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

29
Q

Endocytosis of attached HBV virion followed by

A

release of nucleocapsid and entry into the nucleus

30
Q

Release of HBV genome from

A

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

31
Q

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

A
  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
32
Q

Original HBV vaccines consisted of:

A

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

33
Q

New HBV vaccines are produced using:

A

recombinant yeast cells containing the gene for the S protein.

34
Q

Vaccination programs have been successful in

A

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

35
Q

Alpha-interferon has been used for some years to

A

treat HBV-infected persons.

36
Q

c treatment does not

A

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

37
Q

Alpha-interferon side-effects:

A

influenza-like symptoms and weight loss

38
Q

an improvement over α-interferon =

A

The drug Lamivudine (HIV treatment)

39
Q

Lamivudine =

target =

A

a nucleoside analogue, is also used to treat HBV infection

target = P protein

40
Q

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

A
  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.