Beyond model development: murine astrovirus endogenous pathogens of laboratory mice

超越模型开发：实验小鼠的鼠星状病毒内源性病原体

• 批准号: 9165329
• 负责人: Stacey L Schultz-Cherry
• 金额: $ 8.97万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-24 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9165329
• 关键词: 2 year old; Address; Age; Animal Model; Astrovirus; Biomedical Research; Charge; Child; Core Facility; Diarrhea; Disease; Elderly; Encephalitis; Ensure; Feces; Genotype; Goals; Hospitals; Human; Immune response; Immunocompromised Host; In Vitro; Infection; Influenza; Intestines; Intussusception; Laboratories; Laboratory Study; Laboratory mice; Meleagris gallopavo; Modeling; Mus; Necrotizing Enterocolitis; Norovirus; Oral; Pathogenesis; Pathology; Premature Infant; Prevalence; Public Health; Qualifying; Research; Resources; Source; System; Testing; Therapeutic; Tropism; Turkey bird; Vaccines; Virus; Virus Shedding; age related; animal care; combat; in vivo; interest; microbiome; model development; pathogen; success; therapeutic development; tool

OVERALL ABSTRACT Astrovirus research has been crippled by the lack of in vitro and in vivo propagation systems, precluding not only basic studies of these emerging viruses of increasing public health concern but also posing a major hurdle to vaccine and therapeutics development. Recently, our group and others found that laboratory mice in many facilities, including the most common commercial sources, are infected with murine astroviruses (MuAstV). Like murine norovirus (MNV), MuAstV is highly infectious and can rapidly spread through a colony. Even in immunocompotent mice, the virus can go systemic. The goals of these studies are to develop this model to advance the astrovirus field. More importantly, we will determine if these underlying infections impact biomedical research. The overarching hypothesis is that MuAstV will provide an important new model for astrovirus pathogenesis, immune response, and therapeutics. Further, these seemingly common murine pathogens may impact subsequent research. To address this hypothesis, our Specific Aims are to: 1. Characterize the MuAstV model 2. Determine the impact of asymptomatic MuAstV infection on biomedical research Importantly, my laboratory has the necessary expertise to accomplish the proposed aims having developed the only “small” animal model for astrovirus pathogenesis; baby turkeys infected with turkey astrovirus. Further, we have already produced the necessary tools to define the MuAstV model. A unique strength of our project is access to strong core facilities at St Jude Children's Research hospital including microbiome and animal care resources to rederive murine colonies at no charge if necessary. Collectively, this ensures success of the proposed projects. This overall research plan will have tremendous impact on our ability to combat these highly prevalent human pathogens.

总体摘要 由于缺乏体外和体内繁殖系统，星状病毒的研究一直受到阻碍，排除了 只有对这些新出现的病毒的基础研究日益引起公共卫生的关注，但也构成了一个主要障碍 疫苗和治疗学的发展。最近，我们团队和其他人发现，实验室里的许多老鼠 设施，包括最常见的商业来源，都感染了小鼠星状病毒(MuAstV)。 与鼠诺沃克病毒(MNV)一样，MuAstV具有很高的传染性，可以通过群体迅速传播。即使是在 免疫能力强的小鼠，病毒可以全身感染。这些研究的目标是将这一模式发展为 推进星际病毒场。更重要的是，我们将确定这些潜在感染是否会影响 生物医学研究。最重要的假设是MuAstV将提供一个重要的新模型 用于星状病毒的发病机制、免疫反应和治疗。此外，这些看似常见的 老鼠的病原体可能会影响后续的研究。为了解决这一假设，我们的具体目标是： 1.刻画MuAstV模型 2.确定无症状MuAstV感染对生物医学研究的影响 重要的是，我的实验室拥有必要的专业知识来实现拟议的目标，开发了 星状病毒致病的动物模型只是小的；火鸡幼崽感染了火鸡星状病毒。此外，我们 已经开发出必要的工具来定义MuAstV模型。我们项目的一个独特优势是 获得圣裘德儿童研究医院强大的核心设施，包括微生物群和动物护理 如有必要，免费提供资源，以重新获得小鼠的克隆。总体而言，这确保了 建议的项目。这一总体研究计划将对我们高度打击这些问题的能力产生巨大影响 流行的人类病原体。