Papillomaviridae

1. Papillomaviridae • Properties of Papillomaviruses • Non enveloped icosahedral viroions, 55 nm in diameter • Genome consists of circular double stranded DNA • Papillomaviruses HAVE NOT been grown in culture, but or • Causes will transform cultured cells • Genus – Papillomavirus • Papilli – pustule • Oma – tumor • Causes warts in their natural hosts • Papillomaviruses are resistant to ether, high temperatures, and low pH

2. Papillomaviridae Diseases • Cutaneous papilloma at left • Viruses • Bovine papillomavirus 1 and 2 • Cause cutaneous fibropapilloma in cattle and sarcoid in horses • Bovine pap 3 causes cutaneous papilloma in cattle • Bovine pap 4 causes intestinal tract papilloma in cattle • Bovine pap 5 causes teat fibropapilloma in cattle • Bovine pap 6 causes teat papilloma in cattle

3. Papillomavirus Diseases • Fibropapilloma at left • Equine pap 1 and 2 cause cutaneous papilloma in horses • Canine oral papillomavirus causes oral papilloma • Porcine genital papillomavirus causes cutaneous papilloma in swine • Ovine papillomavirus in sheep • Cottontail rabbit papillomavirus or Shope papillomavirus and rabbit papillomavirus cause cutaneous papilloma in rabbits • Human papillomavirus more than 77 types – cutaneous and mucosal papillomas in humans • Avian papillomavirus – papilloma in parrots

4. Papillomatosis • Fibropapilloma at left • Papillomaviruses produce warts on the skina dn mucouse memmbranes in mah different species. • Only those affecting Cattle, horses and dogs are of veterinary significance (in this course). • Papillomaviruses are usually species and site specific. Serologic crossreactivity has not been detected among papillomaviruses of different species. • Papillomas develop after the introduction of virus through abrasions of the skin

5. Pathogenesis • Virus infection initially occurs in the ACTIVELY DIVIDING BASAL CELLS IN THE STRATUM GERMINATIVUM. • Virus-induced hyperplasia – due to a virus encoded protein – results in increased basal cell division and delayed maturation of cells in the stratum spinosum • The cells subsequently undergo degeneration and hyperkeratinization, aggregating into nascent papillomas • Virus accumulation and associated cytopathology are most noticeable in the stratum granulosum. • Virions are shed with exfoliated cells of the stratum corneum of the skin or non-keratinized cells of the mucosal surfaces

6. Pathogenesis- General and Bovine Papillomatosis • Most warts usually regress spontaneously within 4-6 months • Multiple warts regress spontaneously • The level of neutralizing antibody appears to be correlated with the regression of lesions and with protection against infection • BOVINE PAPILLOMATOSIS – • Warts are more commonly seen in cattle than in any other domestic animal • All ages susceptible - Incidence highest in calves and yearlings • Etiologic agents – Bovine papillomaviruses 1-6 • DO NOT CROSS PROTECT • Types 1,2,5 – Immunologically related. Cause fibropapillomas • Types 3,4,6 – The cause mostly cutaneous papillomas

7. Bovine Papillomatosis and Fibropapilloma • Transmission – • Fomites – halters, nose leads • Grooming and earmarking equipment • Rubbing posts etc. • Venereal – Papilloma seen on the end of the penis of bulls and in the vagina of cows • Clinical Features – IP 4-8 weeks • Fibropapilloma – fibrous core covered with stratified squamous epithelium, outer layers hyperkeratiniized • Lesions vary in size – nodules to cauliflower-like growths – VERRUCA VULGARIS GROWTHS • Usually regress in 6-12 months • Most common on head, neck and shoulders but can be found on udder, teats and genitalia • Young bulls – found on penis NOT prepuce – may interfere with reproduction as bull studs

8. Bovine Papillomatosis and Cutaneous Papilloma • Cutaneous papilloma – lack fibrous core, usually flat with a broad base – • Persistent • Papillomas due to bovine Papillomavirus 4 – alimentary tract, urinary tract • May progress to Squamous Cell Carcinomas • Ingestion of the BRACKEN FERN - PTERIDIUM AQUILINUM appears to be a major contributing factor as a co-carcinogen and immunosuppressive agent in the transition from benign papilloma to invasive carcinoma of the alimentary tract or bladder – chronic endemic hematuria • Diagnosis – characteristic lesions • Virus particles can be demonstrated in lesion biopsies by TEM or detection using PCR

9. Bovine Papillomatosis – Cutaneous form – Type 4- Vaccine with variable results • Treatment – • Lesions that must be removed for aesthetic/health reasons • Surgical excision, cryosurgery with liquid nitrogen is very effective • Dry ice may also be used – CO2 @ -80 degrees C. • Topical agents may be tried when surgery is not possible • Podophyllin 50%, or 2% podophyllin in 25% salicyclic acid and undiluted medical grade DMSO ( CARCINOGENIC!!!). • They are usually applied once daily until remission occurs • Bovine interferon – alpha has been used to treat cattle

10. Canine Oral Papillomatosis • Oral papillomatosis • Contagious, self-limiting disease affecting the oral cavity of young dogs • Can involve all young dogs in a kennel • IP – 4-8 weeks • Warts begins as smooth white elevations – lips • Progress to roughened cauliflower like growths • Occur anywhere on the oral mucosa – cheeks, tongue, palate, pharynx BUT NOT PAST the epiglottis or into the esophagus • Halitosis, hemorrhage, ptylasim and discomfort observed • Many 50-100 may affect mastication and swallowing

11. Canine Oral Papillomatosis –Vaccines can be used • Spontaneous regression is the norm, however, some may persist indefinitely • Secondary bacterial infection of such ulcerated warts may occur • Ocular warts – occur on the conjunctivae, cornea and eyelid margins • Dogs that have recovered from a crop of warts are refractory to infection • Treatment – surgical excision, cryosurgery, electrosurgery may be used • Autogenous vaccines may be used – Effective?

12. Equine Papillomatosis and Sarcoids • Warts are small, elevated, keratinized papillomas around the lips, muzzle, external nares and legs • Ages 1-3 • Range in number from a few to hundreds • Growth occurs for 4-8 weeks and then in most horses, warts spontaneously regress within 1-9 months • Treatment and control is the same as Cattle • Sarcoids – most common skin tumor occurring in horses, donkeys and mules • No apparent predilection for sex, age, breed, coat color or season • Associated with Bovine Papillomavirus 1 and 2 • Sarcoids are often multiple, on lower legs, head and ventral abdoment • Growths may reach the size of a man’s fist, variable in lshape and bulge under skin • Skin is thick, rough and may be ulcerated

13. Equine Papillomatosis and Sarcoids • They DO NOT metastasize BUT persist for life and are locally invasive • Often they recur after surgical removal – difficulty in identifying the junction of the sarcoid with the surrounding tissues • Diagnosis – • Clinical features and histological examination of biopsy material • Treatment – surgical resection – NEVER REGRESS – hyperthermia, laser surgery and cryosurgery

14. Preparing Equine and Bovine Vaccines • Grind up crop of warts, dilute in 1:10 in salien and filter through gauze • Centrifuge solution at 300 rpm for 5 minutesl • Formaldehyde is added to the supernatant fluid to a final concentration of 0.5% formaldehyde • Vaccine can be stored for up to 4 weeks at 4 degrees C • Cattle – inject 5-25 mL (depending on size of animal) SQ can repeat 10-14 days later • Horses – Inject 2 mL ID at 14-day intervals for 3-4 injections