Rabbitpox virus and vaccinia virus infection of rabbits as a model for human smallpox
Rabbitpox virus and vaccinia virus infection of rabbits as a model for human smallpox
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DOI：
10.1128/jvi.00423-07
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发表时间：
2007-10-01
影响因子：
5.4
通讯作者：
Moyer, R. W.
中科院分区：
文献类型：
--
作者：
Adams, Mathew M.;Rice, Amanda D.;Moyer, R. W.
天花的释放和作为生物武器使用的威胁鼓励了对新疫苗和抗病毒药物的研究，以及开发新的小动物模型，以确定其功效。在这里，我们重新调查的兔模型中，皮内感染的兔子非常低剂量的兔痘病毒（RPV）或牛痘病毒西部储备（VV-WR）重演了许多人天花的临床特征。皮内接种RPV后，家兔发生全身性疾病，其特征为广泛的病毒血症、皮肤和皮肤粘膜组织上的许多继发性病变、严重的呼吸道疾病、感染后9天死亡，以及重要的是动物之间的自然气溶胶传播。与以前的报道相反，VV-WR的皮内感染也导致了兔子非常相似的致死性全身性疾病，同样是动物之间的自然气溶胶传播。当哨兵动物和指示动物共养时，两种病毒的传播率均接近100%，哨兵动物也表现出类似的严重疾病。当索引动物和哨兵动物分别饲养在单独的笼子中时，观察到较低的传播率。感染RPV的哨兵动物除一只外均死于该病。然而，大多数VV-WR感染的哨兵动物虽然病情严重，但仍存活下来。最后，我们测试了药物1-O-十六烷氧基丙基-西多福韦在RPV/兔模型中的功效，发现从感染前1天开始每天两次口服剂量为5 mg/kg，持续5天，能够完全保护兔免于致死性疾病。
The threat of smallpox release and use as a bioweapon has encouraged the search for new vaccines and antiviral drugs, as well as development of new small-animal models in which their efficacy can be determined. Here, we reinvestigate a rabbit model in which the intradermal infection of rabbits with very low doses of either rabbitpox virus (RPV) or vaccinia virus Western Reserve (VV-WR) recapitulates many of the clinical features of human smallpox. Following intradermal inoculation with RPV, rabbits develop systemic disease characterized by extensive viremia, numerous secondary lesions on the skin and mucocutaneous tissues, severe respiratory disease, death by 9 days postinfection, and, importantly, natural aerosol transmission between animals. Contrary to previous reports, intradermal infection with VV-WR also resulted in a very similar lethal systemic disease in rabbits, again with natural aerosol transmission between animals. When sentinel and index animals were cohoused, transmission rates approached 100% with either virus, with sentinel animals exhibiting a similar, severe disease. Lower rates of transmission were observed when index and sentinel animals were housed in separate cages. Sentinel animals infected with RPV with one exception succumbed to the disease. However, the majority of VV-WR-infected sentinel animals, while becoming seriously ill, survived. Finally, we tested the efficacy of the drug 1-O-hexadecyloxypropyl-cidofovir in the RPV/rabbit model and found that an oral dose of 5 mg/kg twice a day for 5 days beginning 1 day before infection was able to completely protect rabbits from lethal disease.