Pathogenesis of Vaccinia virus keratitis

痘苗病毒性角膜炎的发病机制

• 批准号: 8287222
• 负责人: Curtis R Brandt
• 金额: $ 18.81万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8287222
• 关键词: Accounting; Animals; Attenuated; B-Lymphocytes; Biological; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Centers for Disease Control and Prevention (U.S.); Conjunctivitis; Cornea; Data; Disease; Disease Outbreaks; Exudate; Eye Infections; Future; Goals; Herpesvirus 1; Human; Immunology; Infection; Inflammatory; Keratitis; Life; Military Personnel; Modeling; Monkeypox; Mouse Strains; Mus; Oryctolagus cuniculus; Outcome; Paper; Pathogenesis; Pathology; Poxviridae; Publishing; Pus; Reagent; Regimen; Russia; Severity of illness; Simplexvirus; Smallpox; Smallpox Vaccine; Steroids; System; Testing; Therapeutic; Tissues; USSR; United States; Vaccination; Vaccines; Vaccinia; Vaccinia virus; Vaccinium; Viral; Virus; Virus Diseases; base; cytokine; emergency service responder; macrophage; mouse model; neutrophil; novel; prednisolone; response; weapons

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.

描述（由申请人提供）：尽管天花不再自然循环，但它仍然是一种潜在的威胁，作为生物武器。目前，天花被美国列为最重要的病毒生物武器。结果，2001年，美国恢复了对第一响应者（例如ER人员）和军队的天花疫苗接种。天花疫苗疫苗病毒是一种活的减毒病毒，不良疫苗反应很常见。此外，动物痘病毒的暴发偶尔发生在人类中。随之而来的结膜炎和角膜炎，可能是盲目的疾病，有可能感染眼睛的眼睛， 可以在疫苗接种或人畜共患病转移后发生。实际上，关于疫苗眼感染或其他痘病毒眼感染的病理机制几乎一无所知。以前，我们开发了一种定量兔病毒角膜炎模型，并表明将局部类固醇纳入治疗可能是危险的。在所有接受泼尼松龙的组中，角膜炎在停止治疗后的3-4天内反弹，这与恢复病毒复制有关。小鼠模型更适合于疫苗感染的病理学和免疫学研究，这是由于试剂的可用性。因此，该R21应用的目的是开发一种新型的牛ac病毒眼感染的定量小鼠模型。 公共卫生相关性：天花疫苗疫苗病毒是一种活的减毒病毒，不良疫苗反应很常见。此外，动物痘病毒的暴发偶尔发生在人类中。实际上，关于疫苗眼感染或其他痘病毒眼感染的病理机制几乎一无所知。小鼠模型更适合于疫苗感染的病理学和免疫学研究，因此目的是开发一种新型的疫苗病毒眼感染的定量小鼠模型。