Beyond model development: murine astrovirus endogenous pathogens of laboratory mice

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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.