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.

项目概要 全球病毒组极其多样化，新出现的病毒威胁着全球健康。不幸的是，感染人数很少 模型可以概括自然传播和进化。在这里，我们建议连接自然和实验 研究宿主内部和宿主之间的实时传播动态并推断病毒病原体的系统 关系。为了实现这一目标，我们将利用一个模型，利用来自宠物店的天然啮齿动物病原体 小鼠接触实验室小鼠、大鼠、仓鼠或鹿鼠。该模型提供了一个学习平台 病毒通过自然机制在宿主之间和宿主内急性传播。这样做的一大优点 模型是你可以访问整个传播链，从储存组织到脱落的东西，再到什么东西 在新主机中复制成功或失败。该提案的目标 1 将检验以下假设：持续时间 暴露、干扰素和感染阶段在储存型病毒传播和进化中的影响。为了这个目标 我们将解决粪便、口腔和呼吸道传播问题。该提案的目标 2 将检验以下假设： 进化距离和干扰素决定跨物种传播事件的成功。致地址 我们将使用 wt 和 STAT2 缺陷的大鼠、仓鼠和鹿小鼠。重要的是，该提案将产生 STAT2 缺陷大鼠。目前，不存在先天性免疫缺陷大鼠，该提案将提供 该领域的宝贵工具。我们将测量天然小鼠病毒跨越物种屏障的能力 并确定进化距离和先天抗病毒反应的影响。总体而言，该提案将 开发和利用模型系统可以分析天然啮齿动物病毒的传播 描述人畜共患疾病的生物屏障的特征。