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Polyomaviruses Flashcards

1
Q

What family is polyomaviruses part of?

A

Polyomaviridae

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2
Q

Do polyomaviruses have envelopes?

A

No

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3
Q

Describe the virion of polyomaviruses?

A

Non-enveloped, 40-45nm, icosahedral

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4
Q

Polyomaviruses: What direction in DNA replication?

A

Bidirectional from a. Unique origin of replication

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5
Q

How many proteins are encoded in polyomaviruses?

A

5-9 viral proteins

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6
Q

What is the host range for polyomaviruses?

A

Mammals, birds, fish

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7
Q

PyV: Early and late transcripts are encoded on ___ DNA strands

A

Opposite

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8
Q

What is the link between SV40 and the vaccine?

A

Early batches of polyomyelitis vaccine were contaminated with SV40

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9
Q

Does SV40 cause cancer in rodents, monkeys, and humans?

A

Monkeys: replicates in kidneys without disease
Rodents: cancer in laboratory conditions
Humans: SV40 found in some cancers but no clear evidence of causal relationship

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10
Q

True or false: SV40 can be lytic and lysogenic

A

True

Infection in permissive cells: new virions and cell lysis
Abortive infection in non-permissive cells: result in transformation of cells

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11
Q

SV40: What is needed for cells to transform?

A

Expression of LTAg and STAg

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12
Q

What are the two PyVs identified?

A

BKPyV and JcPyV

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13
Q

How do BKPyV and JCPyV affect healthy children?

A

Primary infection
Causing mild illness
Through oral route

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14
Q

Describe latent infection of BKPyV and JCPyV and location

A

Establish life-long latency in immune privileged sites like the proximal renal tubes. 80-90% of people persistently infected

No disease during latency

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15
Q

When do JCPyV and BKPyV reactivate

A

Upon immunosuppression

Leads to productive lytic replication

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16
Q

BKPyV reactivating in common in …

A

Kidney transplant patients

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17
Q

BKPyV: lytic viral replication can result in …

A

Acute kidney injury, PVAN, and allograft loss

Haemorrhagic cystitis in bone marrow transplant patients

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18
Q

What is PVAN?

A

Polyomavirus-associated nephropathy

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19
Q

What are early symptoms of BKPyV?

A

Appearance of virus in urine (viruria) and blood (viremia)

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20
Q

What is the only treatment for PVAN?

A

Reduction of immunosuppression

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21
Q

What is a clear sign of BKPyV?

A

Immunohistochemical detection of LTAg

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22
Q

What is PML?

A

Progressive multi focal leukoencephalopathy

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23
Q

PML is caused by …

A

JCPyV

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24
Q

What is PML?

A

Demyelination disease of the CNS
Leads to progressive destruction of the white matter of the brain

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25
PML is seen in…
AIDS patients, and multiple sclerosis patients treated with natalizumab (anti-integrin mAb drug)
26
How does JCPyV reach the brain?
Infecting B cells (leukocytes)
27
Productive replication of JCPyV in ____, the myelinated cells of the CNS, leads to their ____ and to _____
Oligodendrocytes Lysis PML
28
The JCPyV ___ is rearranged in PML, by deletions/duplication of DNA sequence blocks. The non-rearranged JCPyV is known as ____ and the rearranged ones as ____
NCRR Archetype Prototype
29
What are the four PyVs associated with cancer?
BKPyV, JCPyV, MCPyV, TSPyV
30
What is the only PyV identified as a human carcinogen?
MCPyV
31
What is MCC?
Merkel cell carcinoma Rare and aggressive skin cancer 80% cases caused by MCPyV
32
What are Merkel cells?
Neuroendocrine cells at the base of the epidermis Close to nerve endings and sense light touch
33
What are the two aberrant events that contribute to MCC?
Integration of viral genome into host DNA Truncation/mutations in LTAg that impairs its DNA replication activity but keeps its transforming activity
34
What does LTAg do in MCPyV?
Inhibits pRb Cooperates with STAg to transform Merkel cells into MCC cells
35
___ transcribes polyomavirus genome?
Host RNA pol II
36
What does the early region of the polyomavirus encode?
Alternatively spliced LTAg and STAg
37
What does the late region of the polyomavirus genome encode for?
Capsid proteins VP1, VP2, and VP3
38
The non-coding regulatory/control region (NCRR or NCCR) in a polyomavirus contains…
Early and late promoters The origin of viral DNA replication (ori)
39
How do we determine a new species of polyomavirus?
LTAg sequence differs by more than 15% to known species
40
How many genera and species are there in polyomaviruses?
More than 100 species 6 genera (alpha, beta, delta, gamma, zeta)
41
SV40 is part of which genus and species?
Beta Macaca mulatta polyomavirus 1
42
What genus is species does MPyV belong to?
Alpha Mus musculus polyomavirus 1
43
BKPyV is part of which genus and species?
Beta Human polyomavirus 1
44
What is LTAg in polyomavirus?
Oncogene Involved in cellular proliferation (entry in S phase) and transformation Hexamer is DNA helicase needed for viral DNA replication Transcription factor that regulates the switch from early to late gene transcription
45
How does LTAg promote cellular proliferation and transformation?
Interacting with host proteins - Hsc70 chaperone via the J-domain -pRb and related family members p107 and p130, via the LxCxE motif. These interactions release active E2F to promote S-phase entry -p53, via the helicase/p53-binding domain. Prevents apoptosis
46
What is the domain structure of SV40 LTAg?
JD: J-domain: binds to host HSc70 chaperone and stimulates its activity LxCxE/pRb: Rb-binding motif. Binds host pRb, p107 and p130 NLS: Nuclear localization signal: interacts with host importing OBD: Origin-binding domain. Binds to sites in the origin of DNA replication Helicase/p53: Domain with DNA helicase activity and domain that binds to host p53 HR: Host range region
47
What is needed for the transformation activity of LTAg?
N-terminal region: JD, LxCxE/Rb-binding motif Sometimes p-53 binding domain needed
48
The only viral protein required for genome replication in PyV is…
LTAg
49
Describe the structure and function of STAg.
Shares an N-terminal J-domain with LTAg (overlapping coding sequence) Helps LTAg, can’t transform cells by itself except for in MCPyV Activates expression of genes needed for S phase entry and progression. Activity of STAg depends on its interaction with host phosphatase PP2A. Active form of PP2A consists of a heterotrimer STAg replaces the substrate-targeting B subunit, inactivating the enzyme
50
Describe icosahedral symmetry of PyV
T=7 icosahedral symmetry 72 pentamers of VP1 (12 pentamers with 5 neighbours, 60 pentamers with 6 neighbours)
51
Important: PyV: Pentamers interact via the C-terminal portion of VP1 and are further stabilized by ….
Pentamers interact via the C-terminal portion of VP1 and are further stabilized by calcium ions and disulfide bonds between them
52
SV40 entry: SV40 binds to ____ which triggers _____. SV40 moves to ____ and is targeted to the _____. Then enters into the _____ and then moves to _____. Genome is released for transcription and translation
GM1 gangliosides Caveolae-dependent endocytosis Endosomes ER Cytosol Nucleus
53
What are the attachment factors commonly used by polyomaviruses?
All PyV use sialic acid-containing receptors for attachment Glycosaminoglycans Integrity Gangliosides
54
What are sialic acid-containing receptors?
Glycoproteins or glycolipids with attached mono or oligosaccharides and terminal sialic residues
55
What are glycosaminoglycans?
Contain repeating disaccharides and are attached to the polysaccharide sugar core by link proteins
56
What are integrins?
Heterodimeric proteins comprised of alpha and beta chains Contain beta propeller domain, thigh and calf domain, and epidermal growth factor binding domains
57
What are gangliosides?
Glycosphingolipids with ceramide embedded in the membrane and an oligosaccharide chain with one or more sialic acids May also contain a terminal sialic acid
58
____ is the only PyV that uses clathrin-mediated endocytosis
JCPyV
59
SV40, MPyV, and MCPyV use ____ endocytosis and or ____ to enter the cell. JCPyV and BKPyV may also use ____ to enter cells.
Caveolin-mediated endocytosis Non-clathrin/non-caveolin lipid raft uptake mechanisms Extracellular vesicles
60
What attaches to the ganglioside receptor for PyV?
VP1
61
PyV vesicle translocates to the ER through…
Microtubules
62
In the ER, the PyV virion’s capsid structure is destabilized by…
Host disulfide isomerases
63
In the cytoplasm, the PyV virion loses VP1 due to…
Low calcium conditions of the cytosol

MIMM 324 (10 decks)

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