Families: Papillomaviridae and Polyomaviridae Flashcards
What are the main 2 outcomes of Papillomavirus infection?
- formation of benign warts
- hyperplastic epithelial proliferation of the skin or mucous membrane that can undergo malignant transformation
What is the structure of Papillomavirus like? What is its genome like?
non-enveloped, small, icosahedral capsid
single molecule of circular dsDNA associated with histones in chromatin-like complexes
What are the early and late open reading frames in Papillomavirus genome for?
EARLY: express regulatory proteins E1-E8 that a necessary for host cell transformation
LATE: express capsid proteins L1 and L2
What are the 4 steps of Papillomavirus pathogenesis?
- inoculation of epithelium of hand, foot, throat, or cervix
- local multiplication
- wart formation
- wart either resolves (latency) or transforms
What is the most common STI in humans? How do most people present? What are some other possibilities?
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
How is HPV-caused cervical cancer avoided?
recombinant virus-like particle vaccines
- Gardasil
- Cervarix
pap smear
surgery
How does Papillomavirus replicate within the epidermis?
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
HPV lifecycle in epidermis:
What is the mechanism of Papillomavirus oncogenesis? How is the oncogenic potential of BPV determined?
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
How is Papillomavirus able to get into the skin? Where does primary infection start and how does it develop?
entry through skin abrasions or wounds
starts at the stratum germinaticum and proliferates, infecting other keratinocytes laterally in association with virus-induced delayed maturation
How is Papillomavirus infection classified?
heterogenous (affects multiple species
- human, bovine, cottontail rabbit, canine oral, equine, European elk, rabbit oral
How does Bovine Papillomavirus infection typically present? When does this appear?
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
What 2 kinds of Bovine Papillomaviruses cause bovine cutaneous papillomatosis? What lesions characterize each? What aged cows are most susceptible?
BPV-5: flat, rice-grain fibropapilloma
BPV-6: “frond” type teat
calves (sometimes over 2 years old)
What types of BPV are there vaccines created for?
BHV-1, 2, and 4
What are the 2 vaccine strategies against Bovine Papillomavirus?
- 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
- THERAPEUTIC: vaccination of animals infected with BPV-4 E7 or BPV-2 L2 to induce early regression of warts
What is bracken fern poisoning associated with in cows? What causes this?
squamous cell carcinomas - BPV4 acts as a cofactor for cancer development
What is indicative of bracken fern poisoning in cattle?
endophytic growth patterns on the base of the tongue caused by regional LN metastasis to the upper digestive tract
What Papilloma virus is associated with bovine urinary bladder tumors?
BPV-2
How does equine papillomavirus infection present? How does it spread? How does it progress?
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)
What is the most common neoplasm of equids? What causes it?
sarcoids - invasive fibroblastic skin tumor
BPV-1 and BPV-2
What are the 6 types of sarcoid?
- OCCULT - flat, gray, hairless, and persistent; circular
- VERRUSOSE - gray, scabby, or warty; may contain small, solid nodules; possible ulceration
- NODULAR - multiple, discrete, solid nodules of variable size; may ulcerate and bleed
- FIBROBLASTIC - fleshy masses, either with a thin pedicle or a wide, flat base that commonly bleedseasily
- MIXED - variable mixtures of 2 or more types
- MALEVOLENT - RARE, aggressive tumor that spreads extensively through the skin characterized by cords of tumor tissue interspersed with nodules and ulcerating fibroblastic lesions
Equine sarcoid:
What causes oral papillomas in dogs? Cutaneous papillomas?
ORAL: CPV-1, CPV-13
CUTANEOUS: CPV-2, CPV-6
What papillomaviruses cause pigmented plaque growth in dogs? It’s usually not harmful, but what can it progress into?
BPV-3, 4, 5, 7, 8, 9, 10, 11, 12, 14, 15, 16
squamous cell carcinomas
Viral papillomas are rare in cats. What can cause these lesions?
FcaPV-1 —> oral viral papillomas
What are the first papillomavirus shown to cause cancer?
cottontail rabbit papillomavirus (shope papillomavirus)
- squamous cell carcinomas unique to rabbits
What is the genome of Polyomaviridae like? What gene is unique to it?
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
Avian polyomavirus is most devastating in what species? What are are 3 common signs?
Budgerigars (Budgerigar Fledgeling Disease)
- feather dysplasia of primary wing feathers and tail feathers, causing their absence (along with sheaths)
- basophilic intranuclear inclusions in the epithelial cells of the kidney, liver, and ventricles of the brain
- liver necrosis —> ascites, hydropericardium
How does Budgerigar Fledgling Disease differently affect larger psittacines and passerines?
PSITTACINES: mononuclear phagocytic cells with inclusions
PASSERINES: endothelial cells with inclusions
What tropism does goose hemorrhagic polyomavirus have? What is it the causative agent of?
epithelial and endothelial
hemorrhagic nephritis and enteritis of young (2-10 week) geese
What are 5 characteristic lesions of goose hemorrhagic polyomavirus infection?
- nephritis
- depletion of lymphocytes in cloacal bursa
- enteritis
- ascites
- subcutaneous tissue edema
What lab animals are commonly affected by polyomaviruses? What antigen plays an important role?
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
What is Simian Vacuolating virus 40? What is its host range?
non-enveloped, dsDNA virus in the Polymovirus genus of Papovaviridae
humans and nonhuman primates
How is Simian Vacuolating virus 40 able to cause tumors?
it contains the large tumor antigen, T-ag, that is essential for viral replication and cell transformation
In what 4 ways is Simian Vacuolating virus 40 considered an ideal vector?
- can be easily modified to be non-replicative
- can be produced in large quantities
- can infect almost all cell types
- not immunogenic, which allows long-term expression of the transgene
What causes French Moult in budgies? What is the most common sign?
avian polyomavirus
shedding of feathers around the wings and tail
- first feathers to shed will come from the center of the wings
