Pathogenesis of Vaccinia virus keratitis

描述(申请人提供)：尽管天花不再自然传播，但作为生物武器，它仍然是一个潜在的威胁。目前，天花被美国列为最重要的病毒生物武器。因此，在2001年，美国恢复了对急救人员的天花疫苗接种(例如。呃人员)和军队。天花疫苗是一种活的减毒病毒，疫苗的不良反应很常见。此外，动物痘病毒的爆发偶尔也会在人类身上发生。有一种可能性是，眼睛的感染会导致结肠炎和角膜炎，甚至可能是致盲疾病， 可能发生在接种疫苗或人畜共患传播之后。关于痘苗眼部感染或其他痘病毒眼部感染的病理机制，几乎一无所知。在此之前，我们建立了一种定量的兔痘病毒角膜炎模型，并证明了在治疗中加入局部类固醇是潜在的危险。在接受强的松龙治疗的所有组中，角膜炎在停止治疗的3-4天内反弹，这伴随着病毒复制的恢复。由于试剂的可获得性，小鼠模型更适合于研究痘苗病毒感染的病理学和免疫学。因此，R21应用的目标是建立一种新型的定量的小鼠痘苗病毒眼部感染模型。 公共卫生相关性：天花疫苗是一种活的减毒病毒，疫苗不良反应很常见。此外，动物痘病毒的爆发偶尔也会在人类身上发生。关于痘苗眼部感染或其他痘病毒眼部感染的病理机制，几乎一无所知。小鼠模型更适合于研究痘苗病毒感染的病理学和免疫学，因此我们的目标是建立一种新的定量检测痘苗病毒眼部感染的小鼠模型。

DESCRIPTION (provided by applicant): Although Smallpox no longer naturally circulates it remains a potential threat as a biological weapon. Currently, Smallpox is listed as the most important viral bioweapon by the United States. As a result, in 2001, the US resumed smallpox vaccinations for first responders (eg. ER personnel) and the military. The Smallpox vaccine, Vaccinia virus, is a live attenuated virus and adverse vaccine responses are common. In addition, outbreaks of animal pox viruses occasionally occur in humans. There is a possibility that infection of the eye with ensuing conjuncitivitis and keratitis, and perhaps blinding disease, can occur either following vaccination or zoonotic transfer . Virtually nothing is known about pathological mechanisms involved in Vaccinia ocular infections or other poxvirus ocular infections. Previously we developed a quantitative rabbit model of Vaccinia virus keratitis and we showed that the inclusion of topical steroids in therapy was potentially dangerous. In all groups that received prednisolone, keratitis rebounded within 3-4 days of halting the treatment and this was concomitant with the resumption of viral replication. Mouse models are much more suitable for studies on pathology and immunology of Vaccinia infections because of reagent availability. Therefore, the goal of this R21 application is to develop a novel quantitative mouse model of Vaccinia virus ocular infection. PUBLIC HEALTH RELEVANCE: The Smallpox vaccine, Vaccinia virus, is a live attenuated virus and adverse vaccine responses are common. In addition, outbreaks of animal pox viruses occasionally occur in humans. Virtually nothing is known about pathological mechanisms involved in Vaccinia ocular infections or other poxvirus ocular infections. Mouse models are much more suitable for studies on pathology and immunology of Vaccinia infections, thus the goal is to develop a novel quantitative mouse model of Vaccinia virus ocular infection.