Lobe D C, Kreider J W, Phelps W C
Department of Virology, Glaxo Wellcome, Research Triangle Park, NC 27709, USA.
Antiviral Res. 1998 Dec;40(1-2):57-71. doi: 10.1016/s0166-3542(98)00046-1.
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.
克雷德先前的一项研究（克雷德等人，1979年）表明，移植到免疫缺陷裸鼠身上的兔皮能够成功感染棉尾兔乳头瘤病毒（CRPV）。我们在开发一种啮齿动物模型以评估针对乳头瘤病毒的化合物活性方面扩展了这一观察结果。在这个模型（称为SCID-Ra模型）中，将兔耳皮肤移植到SCID小鼠的背部，让其愈合3周。通过划痕感染CRPV会导致超过95%的动物在2至3周内出现疣状病变生长。在感染后（PI）的不同时间可以开始局部和/或全身治疗。记录每周的病变评分，并与未治疗的对照小鼠相比，评估化合物抑制疣生长的能力。利巴韦林在临床上对呼吸道乳头瘤病的治疗以及在兔背部模型中对疣的生长都有抑制作用，对其进行了评估，结果显示口服给药具有显著的抗增殖活性。在这个模型中还评估了包括鬼臼脂和5-氟尿嘧啶在内的抗病毒和抗增殖化合物，这些化合物已在临床上用于治疗人乳头瘤病毒（HPV）感染。在这个系统中评估了用于治疗非小细胞肺癌 的抗有丝分裂化合物诺维本（酒石酸长春瑞滨），结果显示其对疣生长有显著抑制作用，与鬼臼毒素相比，局部细胞毒性稍小。
