Natural model for evaluating within- and cross-species virus transmission

评估物种内和跨物种病毒传播的自然模型

• 批准号: 10735974
• 负责人: Ryan Langlois
• 金额: $ 73.92万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10735974
• 关键词: 2019-nCoV; Acute; Address; Animal Model; Animals; Antiviral Response; Antiviral resistance; Astrovirus; Biological; Biological Models; Consumption; Data; Deer Mouse; Dose; Ebola; Evaluation; Event; Evolution; Excretory function; Exposure to; Failure; Family; Habitats; Hamsters; Human; Immune; Immunity; Immunocompromised Host; Immunologic Deficiency Syndromes; In Vitro; Individual; Infection; Interferons; Laboratories; Laboratory mice; Length; Measures; Methods; Middle East Respiratory Syndrome Coronavirus; Modeling; Murine hepatitis virus; Murine pneumonia virus; Mus; Natural Immunity; Norovirus; Oral; Pathology; Physiological; Population; Population Dynamics; Rattus; Research; Rodent; Rodent Model; Role; Route; STAT2 gene; Sendai virus; Shapes; Signal Transduction; System; Testing; Time; Tissues; Variant; Vertebrate Viruses; Viral; Virus; Work; ZIKA; Zoonoses; cross-species transmission; genetic variant; global health; human migration; human morbidity; human mortality; human pathogen; model organism; pathogen; pathogen spillover; pathogenic virus; prevent; respiratory; success; tool; transcriptome sequencing; transmission process; viral transmission; virome

Project Summary The global virome is incredibly diverse and emerging viruses threaten global health. Unfortunately, few infection models can recapitulate natural transmission and evolution. Here we propose to bridge natural and experimental systems to study real-time transmission dynamics within and between hosts and infer virus-pathogen relationships. To accomplish this we will leverage a model whereby the natural rodent pathogens from pet store mice are exposed to laboratory mice, rats, hamsters, or deer mice. This model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. One major advantage of this model is that you can access the entire transmission chain from the reservoir tissue, to what is shed, to what either succeeds or fails to replicate in the new host. Aim 1 of this proposal will test the hypothesis that the duration of exposure, interferon and stage of infection in the reservoir shape virus transmission and evolution. In this aim we will address fecal oral and respiratory transmission. Aim 2 of this proposal will test the hypothesis that evolutionary distance and interferon determine the success of cross-species transmission events. To address this we will use wt and STAT2 deficient rats, hamsters, and deer mice. Importantly, this proposal will generate STAT2 deficient rats. Currently, there are no innate immune deficient rats exists and this proposal will provide an invaluable tool for the field. We will measure the capacity of natural mouse viruses to cross the species barrier and determine the impact of evolutionary distance and innate antiviral responses. Overall, this proposal will develop and exploit a model system allows for the analysis of transmission of natural rodent viruses to characterize biological barriers to zoonosis.

项目摘要 全球病毒素是多种多样的，新兴的病毒威胁着全球健康。不幸的是，很少感染 模型可以概括自然的传播和进化。在这里，我们建议桥接自然和实验性 研究宿主内外的实时传播动力学的系统，并推断病毒性病毒 关系。为了实现这一目标 小鼠暴露于实验室小鼠，大鼠，仓鼠或鹿小鼠。该模型提供了一个学习的平台 通过自然机制在宿主之间和内部的急性传播病毒。这是一个主要优势 模型是您可以访问从储层组织到棚屋的整个传输链， 成功或无法在新主机中复制。该提案的目标1将检验以下假设 储层病毒传播和进化中的暴露，干扰素和感染阶段。在这个目标中 我们将解决粪便口服和呼吸道传播。该提议的目标2将检验以下假设。 进化距离和干扰素决定了跨物种传输事件的成功。解决 我们将使用WT和STAT2缺乏的大鼠，仓鼠和鹿小鼠。重要的是，该建议将产生 STAT2缺陷大鼠。目前，尚无先天免疫不足的老鼠，该提议将提供 该领域的宝贵工具。我们将测量天然小鼠病毒越过物种屏障的能力 并确定进化距离和先天抗病毒反应的影响。总体而言，该建议将 开发和利用模型系统可以分析自然啮齿动物病毒的传播 描述了人畜共患病的生物障碍。