Test 2- Papillomaviridae Flashcards
Family: Papillomaviridae
General Properties:
Non-enveloped, spherical, 55 nm in diameter, with icosahedral symmetry.
Genome consists of a single molecule of circular double-stranded DNA.
Resistant viruses, survives lipid solvents and detergents, low pH, and high temperatures.
Can transform cultured cells.
- ONCOGENTIC
Papillomaviruses produce
Papillomaviruses produce papillomas (warts) on the skin and mucous membranes of most animal species.
These Warts are benign neoplasms are hyperplastic epithelial outgrowths that generally regress spontaneously.
Are usually species and site specific.
Serologic cross-reactivity has not been detected among papillomaviruses of different species.
Occasionally, however, they may progress to malignancy, which in part is a property of specific virus strains. Example, HPV causing cervical carcinoma in women.
Warts (Benign form)
Malignant
Replication:
Replication of papillomaviruses is linked intimately to the growth and differentiation of cells in stratified squamous epithelium of the skin and some mucous membranes.
Papillomaviruses infect keratinocytes in the basal layer of the epithelium that becomes exposed through micro-wounds.
On infection, the viral genomes are established as low-copy episomes.
The viral genomes are replicated in synchrony with cellular DNA replication.
After cell division, one daughter cell migrates away from the basal layer to outer layers of epidermis and undergoes differentiation.
Differentiation of HPV-positive cells induces the productive phase of the viral life cycle (large number of genome copies), which requires cellular DNA synthesis machinery.
Virus accumulation and associated cytopathology are most noticeable in stratum granulosum.
Virions are shed from the uppermost layers of the epithelium.
The story of Oncogenic Papillomaviruse
In benign warts, the papillomavirus DNA is episomal, meaning it is not integrated into the host-cell DNA and persists as an autonomously replicating episome.
In papillomavirus-induced malignant cancers the viral DNA is integrated into that of the host. Thus, integration probably is necessary for malignant transformation.- VIRUS PRODUCTION STOPS, and VIRUS BECOMES ONCOGENTIC
Integration disrupts one of the early genes, E2, which is a viral repressor.
However, the viral oncogenes (e.g., E6 and E7) remain intact and cause the malignant transformation.
Oncoproteins of Papillomaviruses Papillomavirus (HPV) E6 & E7 proteins
E6 blocks p53(repairs DNA damage)- thus DNA damage can not be repaired or destroyed, so you get get abnormal growth
Bovine Papillomatosis
Host and Transmission
Host: Cattle.
Warts are more commonly seen in cattle than in any other domestic animal.
All ages are susceptible, incidence is highest in calves and yearlings.
Natural bovine papillomavirus infection of horses may occur after exposure of the horses to cattle.
Transmission:
Virus is transmitted between animals by contaminated fomites, such as contaminated milking equipment, halters, nose leads, grooming and earmarking equipment, etc.
Sexual transmission of venereal warts in cattle.
Bovine Papillomatosis
Fibropapilloma
Mostly caused by Bovine papillomavirus types 1, 2, and 5
Papillomas have a fibrous core covered to a variable depth with stratified squamous epithelium, the outer layers of which are hyperkeratinized.
Lesions vary from small firm nodules to large cauliflower-like growths.
Grayish to black in color and rough and spiny to the touch.
Multiple Fibropapillomas
Fibropapilloma
Bovine Papillomatosis
Fibropapilloma:
Fibropapillomas are common on the udder and teats and on the head, neck, and shoulders.
They may also occur in the omasum, vagina, vulva, penis, and anus.
Young bulls: Fibropapillomas are found frequently on the penis, but not on prepuce.
Wart grows rapidly and may surround tip of penis. This may render them of no value as bull studs.
Teat Papillomas
Fibropapilloma of the Glans Penis
Bovine Papillomatosis
Fibropapilloma of the Glans Penis
Cutaneous papilloma
Bovine Papillomatosis Bovine papillomaviruses type 3.
Lesions lack a fibrous core.
Are usually flat (unlike papillomatosis) with a broad base, unlike the more usual fibropapillomas that protrude and are often pedunculated. Lesions tend to persist.
Bovine Papillomatosis
Bracken Fern and Bovine Papillomaviruses:
Bovine papillomavirus 4 can cause transient papillomas in the alimentary tract.
I_ngestion of the bracken fern_ can result in transition to invasive carcinoma of the alimentary tract.
This is because bracken fern contains carcinogens, mutagens, and immunosuppressive chemicals.
_ In cattle that eat bracken fern, papillomavirus typ_es 1 and 2 may also contribute to the syndrome of “enzootic hematuria” that is characterized by hematuria and/or urinary bladder cancer.
Acute Bracken Fern Poisoning Thrombocytopenia with suffuse hemorrhage
Bracken fern
Bovine Papillomatosis
Diagnosis:
Viruses visible in lesion biopsies by TEM.
PCR, DNA hybridization assays.
Bovine Papillomatosis
Treatment:
Treatment:
Surgical excision, or cryosurgery with liquid nitrogen.
Topical agents, Podophyllin and undiluted medical grade DMSO (DiMethylSulfOxide)
Bovine interferon-alpha
VACCINE- WART VACCINE
Canine Oral Papillomatosis
Contagious, self-limiting disease affecting oral cavity of dogs
The warts usually begin on the lips, and can spread to the buccal mucosa, tongue, palate, and pharynx. Later may become roughened and cauliflower-like. Do not extend below epiglottis or into esophagus.
Characterized histologically by epithelial hyperplasia and cytoplasmic vacuolization (koilocytosis)
Lesions typically regress spontaneously
Progression to squamous cell carcinoma occurs very rarely.
Multiple Papillomas on the Lips of a Young Dog
Extensive Oral Papillomatosis
Canine Oral Papillomatosis
Clinical signs:
Halitosis (bad breath), hemorrhage, ptyalism (Hypersalivation), discomfort.
Numerous warts may interfere with mastication and deglutition.
Warts may regress, or secondary bacterial infection and ulceration may occur.
Ocular warts: Conjunctiva, cornea, eyelid margins.
Recovered dogs are refractory to reinfection.
Canine Oral Papillomatosis
Treatment:
Treatment:
Surgical excision, cryosurgery, electrosurgery.
Autogenous Vaccines (a wart is removed, made into a crude vaccine, and injected into the same animal) may be tried. Efficacy doubtful.
Equine Sarcoids
Sarcoids commonly occur in horses, donkeys and mules between 1 to 6 years of age. Most common neoplasm in Horses.
They are locally invasive benign fibroblastic skin tumors.
Associated with bovine papillomaviruses 1 or 2.
Sarcoids do not metastasize. They may persist for life. Are locally invasive. Recur after surgical removal.
Proliferation of dermal fibroblasts and the overlying epidermis
Equine Sarcoids
Transmission:
The mode of transmission has not been confirmed.
Flies act as vectors?
Fomites, transmitted via stable management practices.
Breed susceptibility with major histocompatibility complex has been defined.
Equine Sarcoids
Susceptible Breeds
Arabian Horse
Appaloosa Horse
American Quarter Horse
Equine Sarcoids
Less Susceptible Breeds
Standardbred Horse
Thoroughbred Horse
Equine Sarcoids
Lesions
Lesions commonly occur in traumatized areas.
Single or multiple.
Growths may reach size of man’s feast, bulge under skin.
May become ulcerated.
Palpebral sarcoid—multilobed SC lesion; small nodular lesion in lower lid
Leg Sarcoid
Muzzle Sarcoid
Equine Sarcoids
The clinical appearance of a sarcoid affected wound is often very similar
Equine Sarcoids
The clinical appearance of a sarcoid affected wound is often very similar to “proud flesh” or exuberant granulation tissue.
However, sarcoids are frequently are seen at sites of previous injury and scarring.
Equine Sarcoids
Dx and treatment
Diagnosis:
Clinical features.
Histological examination of biopsy material Virus detection
Treatment:
Cryotherapy, Surgical or Laser excision, and Local immune modulation, Local radiotherapy,
Can also have papillomatosis in
CATS
