Families: Papillomaviridae and Polyomaviridae

Question 1

What are the main 2 outcomes of Papillomavirus infection?

Answer 1

1. formation of benign warts
2. hyperplastic epithelial proliferation of the skin or mucous membrane that can undergo malignant transformation

Question 2

What is the structure of Papillomavirus like? What is its genome like?

Answer 2

non-enveloped, small, icosahedral capsid

single molecule of circular dsDNA associated with histones in chromatin-like complexes

Question 3

What are the early and late open reading frames in Papillomavirus genome for?

Answer 3

EARLY: express regulatory proteins E1-E8 that a necessary for host cell transformation

LATE: express capsid proteins L1 and L2

Question 4

What are the 4 steps of Papillomavirus pathogenesis?

Answer 4

1. inoculation of epithelium of hand, foot, throat, or cervix
2. local multiplication
3. wart formation
4. wart either resolves (latency) or transforms

Question 5

What is the most common STI in humans? How do most people present? What are some other possibilities?

Answer 5

human papillomavirus (HPV)

body’s immune system is able to clear HPV within 2 years, so no symptoms develop

• genital warts
• cervical cancer
• mouth/throat infection

Question 6

How is HPV-caused cervical cancer avoided?

Answer 6

recombinant virus-like particle vaccines
- Gardasil
- Cervarix
pap smear
surgery

Question 7

How does Papillomavirus replicate within the epidermis?

Answer 7

STRATUM SPINOSUM: maintenance of viral DNA (episomal), with few copies per cell

STRATUM GRANULOSUM: early protein synthesis, DNA replication

STRATUM CORNEUM: late (capsid) protein synthesis, virus assembly and maturation

Question 8

HPV lifecycle in epidermis:

Answer 8

Question 9

What is the mechanism of Papillomavirus oncogenesis? How is the oncogenic potential of BPV determined?

Answer 9

NATURAL HOST (cattle + BPV) = self-limited neoplastic disease, including large fibrous skin warts
INCIDENTAL HOST (horse + BPV) = sarcoid

BPV transforms cells by inserting viral genome into the host’s genome, resulting in loss of cellular functions

presence of viral proteins E5, E6, and E7

Question 10

How is Papillomavirus able to get into the skin? Where does primary infection start and how does it develop?

Answer 10

entry through skin abrasions or wounds

starts at the stratum germinaticum and proliferates, infecting other keratinocytes laterally in association with virus-induced delayed maturation

Question 11

How is Papillomavirus infection classified?

Answer 11

heterogenous (affects multiple species

• human, bovine, cottontail rabbit, canine oral, equine, European elk, rabbit oral

Question 12

How does Bovine Papillomavirus infection typically present? When does this appear?

Answer 12

growth of fibropapilloma (warts) on the skin of the head, neck, shoulders, back, venereal regions, and abdomen that begin small and nodular, and then grow rapidly into dry, whitish, cauliflower-like masses

about 2 months after exposure, may last over a year

Question 13

What 2 kinds of Bovine Papillomaviruses cause bovine cutaneous papillomatosis? What lesions characterize each? What aged cows are most susceptible?

Answer 13

BPV-5: flat, rice-grain fibropapilloma
BPV-6: “frond” type teat

calves (sometimes over 2 years old)

Question 14

What types of BPV are there vaccines created for?

Answer 14

BHV-1, 2, and 4

Question 15

What are the 2 vaccine strategies against Bovine Papillomavirus?

Answer 15

1. PROPHYLACTIC: prevent infection in those not affected yet with the whole virus (formalin-killed wart tissue suspension, virus-like particle) that’s ineffective against existing warts
2. THERAPEUTIC: vaccination of animals infected with BPV-4 E7 or BPV-2 L2 to induce early regression of warts

Question 16

What is bracken fern poisoning associated with in cows? What causes this?

Answer 16

squamous cell carcinomas - BPV4 acts as a cofactor for cancer development

Question 17

What is indicative of bracken fern poisoning in cattle?

Answer 17

endophytic growth patterns on the base of the tongue caused by regional LN metastasis to the upper digestive tract

Question 18

What Papilloma virus is associated with bovine urinary bladder tumors?

Answer 18

BPV-2

Question 19

How does equine papillomavirus infection present? How does it spread? How does it progress?

Answer 19

cauliflower-like growth most often on the nose and around the lips of young horses, but can also be found on the inner aspects of the ears

direct contact through wounds or abrasions

self-limiting and disappears spontaneously in 4-8 weeks (natural infection = solid immunity)

Question 20

What is the most common neoplasm of equids? What causes it?

Answer 20

sarcoids - invasive fibroblastic skin tumor

BPV-1 and BPV-2

Question 21

What are the 6 types of sarcoid?

Answer 21

1. OCCULT - flat, gray, hairless, and persistent; circular
2. VERRUSOSE - gray, scabby, or warty; may contain small, solid nodules; possible ulceration
3. NODULAR - multiple, discrete, solid nodules of variable size; may ulcerate and bleed
4. FIBROBLASTIC - fleshy masses, either with a thin pedicle or a wide, flat base that commonly bleedseasily
5. MIXED - variable mixtures of 2 or more types
6. MALEVOLENT - RARE, aggressive tumor that spreads extensively through the skin characterized by cords of tumor tissue interspersed with nodules and ulcerating fibroblastic lesions

Question 22

Equine sarcoid:

Answer 22

Question 23

What causes oral papillomas in dogs? Cutaneous papillomas?

Answer 23

ORAL: CPV-1, CPV-13

CUTANEOUS: CPV-2, CPV-6

Question 24

What papillomaviruses cause pigmented plaque growth in dogs? It’s usually not harmful, but what can it progress into?

Answer 24

BPV-3, 4, 5, 7, 8, 9, 10, 11, 12, 14, 15, 16

squamous cell carcinomas

Question 25

Viral papillomas are rare in cats. What can cause these lesions?

Answer 25

FcaPV-1 ---> oral viral papillomas

Question 26

What are the first papillomavirus shown to cause cancer?

Answer 26

cottontail rabbit papillomavirus (shope papillomavirus) - squamous cell carcinomas unique to rabbits

Question 27

What is the genome of Polyomaviridae like? What gene is unique to it?

Answer 27

circular dsDNA complexed into histones - smaller than Papillomaviridae overprinting gene (ALTO) - allowing it to use a seqment of DNA originally encoding only one protein to express a second, by shifting the reading frame

Question 28

Avian polyomavirus is most devastating in what species? What are are 3 common signs?

Answer 28

Budgerigars (Budgerigar Fledgeling Disease) 1. feather dysplasia of primary wing feathers and tail feathers, causing their absence (along with sheaths) 2. basophilic intranuclear inclusions in the epithelial cells of the kidney, liver, and ventricles of the brain 3. liver necrosis ---> ascites, hydropericardium

Question 29

How does Budgerigar Fledgling Disease differently affect larger psittacines and passerines?

Answer 29

PSITTACINES: mononuclear phagocytic cells with inclusions PASSERINES: endothelial cells with inclusions

Question 30

What tropism does goose hemorrhagic polyomavirus have? What is it the causative agent of?

Answer 30

epithelial and endothelial hemorrhagic nephritis and enteritis of young (2-10 week) geese

Question 31

What are 5 characteristic lesions of goose hemorrhagic polyomavirus infection?

Answer 31

1. nephritis 2. depletion of lymphocytes in cloacal bursa 3. enteritis 4. ascites 5. subcutaneous tissue edema

Question 32

What lab animals are commonly affected by polyomaviruses? What antigen plays an important role?

Answer 32

MICE - K virus, murine pneumotropic virus (MPtV), an ENDOTHELIOTROPIC virus that does NOT primarily target the lungs - can also infect monkeys, rats, hamsters, and rabbts MT antigen activates protein kinases of c-SRc family, which are used in transgenic constructs for tumor induction in genetically engineered mice

Question 33

What is Simian Vacuolating virus 40? What is its host range?

Answer 33

non-enveloped, dsDNA virus in the Polymovirus genus of Papovaviridae humans and nonhuman primates

Question 34

How is Simian Vacuolating virus 40 able to cause tumors?

Answer 34

it contains the large tumor antigen, T-ag, that is essential for viral replication and cell transformation

Question 35

In what 4 ways is Simian Vacuolating virus 40 considered an ideal vector?

Answer 35

1. can be easily modified to be non-replicative 2. can be produced in large quantities 3. can infect almost all cell types 4. not immunogenic, which allows long-term expression of the transgene

Question 36

What causes French Moult in budgies? What is the most common sign?

Answer 36

avian polyomavirus shedding of feathers around the wings and tail - first feathers to shed will come from the center of the wings