Pathogenesis of Vaccinia virus keratitis

项目摘要 虽然天花不再自然传播，但作为一种生物病毒， 武器目前，天花被美国列为最重要的病毒生物武器。 States.因此，在2001年，美国恢复了第一反应者的天花疫苗接种（如。儿 人员）和军队。天花疫苗，即牛痘病毒，是一种减毒活病毒， 不良的疫苗反应是常见的。此外，动物痘病毒的爆发 偶尔也会发生在人类身上。有一种可能性是眼睛的感染， 结膜炎和角膜炎，以及可能致盲的疾病，可在接种疫苗后发生， 或动物传染病。事实上，我们对参与这些疾病的病理机制一无所知。 牛痘眼部感染或其他痘病毒眼部感染。以前我们开发了一个 定量兔模型的牛痘病毒角膜炎，我们表明，包括局部 类固醇治疗有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，这与 恢复病毒复制。小鼠模型更适合于病理学研究 和免疫学的牛痘感染，因为试剂的可用性。因此， 本R21应用是开发一种新的牛痘病毒眼部定量小鼠模型， 感染

Project Summary 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.