Pathogenesis of Vaccinia virus keratitis

描述（由申请人提供）：虽然天花不再自然传播，但它仍然是一种潜在的生物武器威胁。目前，天花被美国列为最重要的病毒性生物武器。因此，在2001年，美国恢复了第一反应者的天花疫苗接种（如。人员）和军队。天花疫苗，牛痘病毒，是一种减毒活病毒，疫苗不良反应是常见的。此外，动物痘病毒偶尔会在人类中爆发。有一种可能性是眼睛感染，随后结膜炎和角膜炎，也许致盲疾病， 可能发生在接种疫苗或人畜共患病转移后。事实上，对牛痘眼部感染或其他痘病毒眼部感染的病理机制一无所知。以前，我们建立了一个牛痘病毒性角膜炎的定量兔模型，我们表明，在治疗中包括局部类固醇是潜在的危险。在接受泼尼松龙的所有组中，角膜炎在停止治疗后3-4天内反弹，这伴随着病毒复制的恢复。小鼠模型更适合于牛痘病毒感染的病理学和免疫学研究，这是因为其试剂易得。因此，该R21申请的目标是开发一种新的牛痘病毒眼部感染的定量小鼠模型。 公共卫生相关性：天花疫苗，牛痘病毒，是一种减毒活病毒，疫苗不良反应很常见。此外，动物痘病毒偶尔会在人类中爆发。事实上，对牛痘眼部感染或其他痘病毒眼部感染的病理机制一无所知。小鼠模型更适合于研究牛痘病毒感染的病理学和免疫学，因此，建立一种新的牛痘病毒眼部感染的定量小鼠模型是研究的目标。

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.