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Published on: March 8, 2012
Therapeutic evaluation of compounds in the SCID-RA papillomavirus model
D C Lobe1, J W Kreider, W C Phelps
1Department of Virology, Glaxo Wellcome, Research Triangle Park, NC 27709, USA.
Abstract:
A previous study by Kreider (Kreider et al., 1979) indicated that rabbit skin, which had been transplanted to immunodeficient nude mice, could be successfully infected with cottontail rabbit papillomavirus (CRPV). We have extended this observation in developing a rodent model for evaluation of compounds for activity against the papillomaviruses. In this model (called the SCID-Ra model), rabbit ear skin is transplanted to the dorsum of SCID mice and allowed to heal for 3 weeks. Infection with CRPV by scarification leads to the growth of warty lesions within 2 3 weeks in >95% of the animals. Topical and/or systemic therapy can be initiated at various times post infection (PI). Weekly lesion scores are recorded and compounds are evaluated for their ability to suppress wart growth when compared to untreated control mice. Ribavirin, which has had a suppressive effect both in the clinic for the treatment of respiratory papillomatosis and on the growth of warts in the rabbit back model, was evaluated and showed significant anti-proliferative activity with oral dosing. Both antiviral and antiproliferative compounds including podophyllin and 5-fluorouracil, which have been used clinically for the treatment of human papillomavirus (HPV) infections, were evaluated in this model. The anti-mitotic compound, Navelbine (vinorelbine tartrate), which is used for the treatment of non-small cell lung carcinoma was evaluated in this system and showed significant inhibition of wart growth with somewhat less topical cytotoxicity when compared to podophyllotoxin.
Insights
A novel SCID-Ra rodent model using rabbit skin on mice effectively models papillomavirus infections. This model demonstrated the anti-proliferative activity of compounds like ribavirin, 5-fluorouracil, and Navelbine against viral warts.
Area of Science:
- Virology
- Dermatology
- Pharmacology
Background:
- Previous studies showed rabbit skin on immunodeficient mice could be infected with cottontail rabbit papillomavirus (CRPV).
- Papillomaviruses cause significant health issues, necessitating effective treatment evaluation models.
Purpose of the Study:
- To develop and validate a SCID-Ra rodent model for evaluating anti-papillomavirus compound efficacy.
- To assess the anti-proliferative and antiviral activities of known and novel compounds against CRPV-induced warts.
Main Methods:
- Rabbit ear skin was transplanted onto SCID mice (SCID-Ra model) and infected with CRPV.
- Lesion development was monitored, and therapeutic compounds were administered topically and/or systemically post-infection.
- Compounds evaluated included ribavirin, podophyllin, 5-fluorouracil, and Navelbine (vinorelbine tartrate).
Main Results:
- The SCID-Ra model demonstrated high susceptibility (>95%) to CRPV infection, producing warty lesions within 2-3 weeks.
- Ribavirin showed significant anti-proliferative activity via oral dosing.
- Navelbine demonstrated significant wart growth inhibition with reduced topical cytotoxicity compared to podophyllotoxin.
Conclusions:
- The SCID-Ra model is a viable and effective rodent system for evaluating anti-papillomavirus therapies.
- Compounds like ribavirin and Navelbine show promise for treating papillomavirus infections, warranting further investigation.
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