Lecture 18 Hepadnaviruses

For the final

Hepadnaviruses

Hepatitis-causing DNA viruses

What is the genomes of hepadnaviruses?

Partially single-stranded DNA

How do hepadnaviruses replicate?

An RNA intermediate

Describe the HBV capsid

Icosahedral

Small holes on the outside

Spikes protrude from surface

Hosts of hepadnaviruses

Humans and other primates

Birds

What can chronic infections of HBV lead to?

Cirrhosis of liver

Hepatocellular carcinoma (HCC) or liver cancer

HBV virion

Roughly spherical

S, M, L envelope proteins

P polymerase protein

cccDNA in HBV

Covalently closed circular DNA

Formed in nucleus of infected liver cells

Hepatocytes

Infected liver cells

Does HBV replication need a primer?

Yes

What is the primer for HBV?

Terminal domain of the P protein (polymerase)

HBV pregenome

3.5 kb

Pregenome RNA acts as template for DNA synthesis

What does the P protein make first for DNA synthesis?

(-)ssDNA

Where is the polymerase located?

In the P protein covalently linked to the 5’ end of (-)ssDNA

T/F: Hepadnaviruses have both infectious and non-infectious particles

True

What are the noninfectious HBV particles?

1) Spherical (small)

2) Filamentous (large)

Where is the attachment site for HBV viruses?

Near the N terminus of the L protein

T/F: All L proteins in HBV have an N terminus

True

T/F: All L proteins in HBV have an N terminus located on the outside

False

What are the surface proteins in HBV?

Small (S), medium (M), and large (L) proteins

Which surface protein is the most abundant?

Small protein (S)

How are HBV genes expressed?

1) 4 promoters

2) 2 enhancers

3) Living-specific factors

What happens once the HBV genome is free in the nucleus?

It’s converted to circular DNA

T/F: HB genomes replicates in the nucleus

False

T/F: HBV DNA integrates into host genome

False

Why can’t HBV DNA integrate into the host’s genome?

There is no integrase activity

How many types of mRNAs are produced in HBV?

5

T/F: All viral mRNAs in HBV have the same 3’ ends

True

T/F: All viral mRNAs across all viruses have the same 3’ ends

False

What is the result of (+)DNA synthesis in HBV?

An incomplete (+)ssDNA in the virion

How many types of proteins are produced by HBV?

7

1) Core (HBcAg)

2,3,4) Surface proteins (S, M, L)

5) e Antigen (HBeAg)

6) Polymerase

7) X protein (HBx)

Core protein in HBV

HBcAg

Forms inner capsid

Packages viral genome

e Antigen in HBV

HBeAg

Secreted from cells

Derived from precore region

X Protein in HBV

HBx

Non-structural protein that helps regulate gene expression & replication

T/F: HBV and HDV use the same cellular responses

True

What does HDV need to replicate?

HBV

How is HBV transmitted?

Blood or semen