Out of the reservoir: identification and characterization of viral and host factors governing the pathobiology of zoonotic cowpox viruses

走出储存库：控制人畜共患牛痘病毒病理学的病毒和宿主因素的识别和表征

• 批准号: 226372197
• 负责人: Professor Dr. Martin Beer
• 金额: --
• 依托单位: Institut für Virologie (WE05)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/226372197?language=en
• 关键词: Out; reservoir; identification; characterization; viral

This is a continuation proposal in which we build on results from the first funding period. Although we were able, for the first time, to isolate and characterize in detail a cowpox virus (CPXV) from the rodent reservoir, the common vole, we are continuing field studies. Our goal is to gain a better understanding of the ecology of CPXV maintenance and transmission within the reservoir, by screening for further isolates with an optimized sampling scheme and by determining seroprevalences in defined habitats. The first vole isolate allowed comparison with available CPXV sequences from accidental/spill-over hosts (rats, cats, cattle). Alterations in virus-encoded proteins were identified that we surmise allow CPXV maintenance in the reservoir and others that are responsible for successful spill-over into accidental hosts. We will here investigate if and how the identified CPXV factors contribute to maintenance in the natural vole reservoir and to spill-overs into different accidental hosts. Importantly, we shall determine how those factors are linked to virulence. The experiments will be done by first creating recombinant and chimeric CPXV that are based on full-length clones and by performing cell biological, biochemical and immunological assays to determine protein function. Among others, we will perform detailed experiments on potentially species-specific CPXV immune evasion proteins (e.g., 7tGP, CrmE and D7L proteins) as well on the possible interference of CPXV with Mx proteins in vole species. We shall cooperate with other groups of SPP1596 based on established cooperations, primarily R.G. Ulrich (screening of voles including prevalence studies), M. Marz (RNAseq analysis and automated annotation of CPXV genomes), K. Kramer-Schadt (ecology and modeling), G. Kochs (role of the vole Mx proteins) and C. Drosten (overall context of zoonotic rodent borne pathogens).

这是一项延续提案，我们在第一个资助期的成果基础上再接再厉。虽然我们第一次能够从啮齿动物宿主--普通田鼠身上分离并详细描述一种牛痘病毒(CPXV)，但我们仍在继续进行实地研究。我们的目标是更好地了解CPXV在水库内的维持和传播的生态，通过优化采样方案筛选更多的分离物，并通过确定确定的栖息地的血清效价。第一个田鼠分离株可以与来自意外/溢出宿主(老鼠、猫、牛)的可用的CPXV序列进行比较。病毒编码蛋白的改变被识别出来，我们推测这允许CPXV在储存库中维持，以及其他负责成功溢出到意外宿主的改变。我们将在这里调查已确定的CPXV因素是否以及如何有助于天然田鼠水库的维护和溢出到不同的意外宿主。重要的是，我们将确定这些因素如何与毒力联系在一起。实验将首先在全长克隆的基础上创造重组和嵌合的CPXV，并进行细胞生物学、生化和免疫学分析以确定蛋白质的功能。其中，我们将对可能具有物种特异性的CPXV免疫逃避蛋白(例如7tgp、crme和D7L蛋白)以及CPXV对田鼠Mx蛋白的可能干扰进行详细的实验。我们将在已建立的合作基础上与SPP1596的其他小组合作，主要是R.G.Ulrich(田鼠筛查包括流行率研究)、M.Marz(RNAseq分析和CPXV基因组的自动注释)、K.Kramer-Schadt(生态学和建模)、G.Kochs(田鼠Mx蛋白的作用)和C.Drosten(人畜共患啮齿动物传播病原体的总体背景)。