Virology - Viruses

polyomavirus - nucleic acid and shape

dsDNA, circular

polyomavirus - baltimore class

I

polyomavirus - enveloped?

No

polyomavirus - virion diameter

45 nm

(Quiz 1) Polyomaviruses genomes are:

circular dsDNA

polyomavirus - replication site

Nucleus

polyomavirus - examples

SV40, BK, JC, Merkel cell

Why are polyomaviruses double the size of parvoviruses?

Polyomaviruses have dsDNA, which is more rigid than parvovirus ssDNA

Persistence length defintion

how “bendy“ a molecule is. Higher value = more rigid

SV40 (simian virus)

• contaminated the polio vaccine

• causes vacuole formation in African Green Monkey kidney cells, but not in Rhesus cells

• in making the polio vaccine, SV40 becomes partially inactivated

• SV40 + hamster cheek pouch = cancer

(Quiz 1) Polyomaviruses enter cells through:

lipid rafts (caveolin-mediated)

Which virus family genomes are coated in histones? (more than one)

Polyomavirus, papillomavirus

(Quiz 1) Which of the following are stages of gene expression for polyoma and papilloma viruses?

late, early

What do polyomaviruses utilize to increase coding capacity?

splicing, ORFs

Early proteins in polyomaviruses help facilitate…

viral genome replication

When are late proteins produced in polyomaviruses and what’s its function?

After viral DNA replication, code for structural proteins

Non Coding Regulatory Region (NCRR) consists of…

ori, early and late promoters, viral enhancer, packaging signal

(Quiz 1) How many origins of replication (ori) do polyomaviruses have in their genome?

1

T-antigen (T-ag) Effect on virus

1) Bind ori to initiate replication

2) Shut off early transcription

3) Activate late transcription

T-antigen (T-ag) Effect on host cell

1) Bind and inactivate Rb and p53

2) Drive cells into S phase

Polyomaviruses: Early and Late Transcription

1) Sp1 transcription factor binds to SV40

2) early transcription with cellular RNA pol » large T-ag expression

3) T-ag binds ori » recruit cellular DNA pol » initiate viral DNA replication

4) T-ag binds ealry promoter » shut off early transcription » promote late transcription

What phase must cells be for small DNA viruses (polyoma/papilloma) to replicate?

S phase

Retinoblastoma (Rb) function

tumor suppressor, suppress transcription

p53 function

tumor suppressor, transcription factor for cell death

Which virus requires T-ag for replication? (1 answer)

polyomavirus

VP4 function

pore-forming protein to lyse cell membrane

Which molecules link each pentamer to the viral genome in polyomaviruses?

VP2 or VP3

(Quiz 1) Which of the followings are a function of the polyomaviruses T-antigen?

• Inactivates p53 and Rb

• Shuts off early gene transcription and promotes late gene transcription

• Drive cells into S phase

• Binds the viral ori to initiate viral DNA replication

(Quiz 1) Cancer associated with polyomaviruses infection is a mistake from the point of view of the virus

true

What type of cells allows polyomaviruses to integrate into host genomes?

non-permissive cells

Which polyomaviruses are associated with some cancers? (more than 1)

JK, BK

Which polyomaviruses have a causal link with some cancers? (1 answer only)

Merkel Cell Carcinoma

In what part of the body is Merkel cell carcinoma more likely to occur?

Merkel cells in basal layer and sun-exposed skin

In tumor cells MCPyV are often clonal, meaning…

tumor cells have identical genome integration site

(Quiz 1) A key event in the development of Merkel Cell Carcinoma is:

 

Truncation of MCPyV T-antigen

In MCPyV integrated genomes, what prevents viral replication?

mutations in T-ag

Summary of MCPyV (Merkel cell)

• most cases of MCC has clonal integration of MCPyV with mutated T-ag

• MCC risk increase with age, males, sun exposure…

• MCPyV is a common infectious agent (40-90% population infected), but MCC is a rare condition

papillomavirus - nucleid acid and shape

dsDNA, circular

papillomavirus - Baltimore class

I

papillomavirus - enveloped?

No

papillomavirus - Virion diameter

50 nm

papillomavirus - Genome

8k bp

papillomavirus - Replication site

Nucleus

papillomavirus - examples

HPV (many serotypes)

serotype definition

group of cells identified by differing antigens or other molecular differences

How many strand(s) of the HPV genome is transcribed?

1

How many early ORFs and late ORFs in HPV?

7 early, 2 late

How many origins of replication (ori) do papillomaviruses have in their genome? 

1

What do papillomaviruses utilize to increase coding capacity?

alternative splicing

What cells do HPV infect and become activated?

differentiating basal cells

(Quiz 1) Which proteins in papillomaviruses have the same role as T-ag in polyomaviruses?

E6, E7

(Quiz 1) Integration into the host genome is a necssary part of the HPV life cycle

false

Can HPV cause cancers?

yes

HPV vaccines

• virus-like particles

• non-infectious

• lead to high levels of antibodies

Can HPV integrate into the host cell genome and is it a mistake?

yes, yes

After integration, can HPV replicate and initiate cell lysis?

No. It allows E6 and E7 expression, but loses genes for replication and cell lysis

(Quiz 1) Which of the following is true for papillomaviruses but not polyomaviruses?

latent infection, have a vaccine