Hantaviruses: crossing the species barrier of natural hosts

汉坦病毒(Bunyaviridae)是引起人类两种人畜共患病的新病毒，肾综合征出血热和汉坦病毒心肺综合征，以其与宿主(主要是啮齿动物)的密切联系而闻名。然而，所谓的非宿主动物的溢出感染在自然界中发生，并可能为汉坦病毒的物种屏障机制和病毒宿主转换过程提供重要的见解。这项建议侧重于对德国现有的三种汉坦病毒的自然感染和溢出感染进行比较分析，这三种病毒分别是由岸鼠(Myodes Tarreolus)携带的Puumala病毒(PUUV)，由黑线姬鼠(Apodemus Agrarius)携带的多布拉瓦-贝尔格莱德病毒(DOBV)，以及由普通田鼠(Microtus Arvalis)和相关田鼠物种携带的图拉病毒(TULV)。将对共生啮齿动物物种(包括水库和非水库物种)的研究与体外实验相结合，将有助于研究宿主物种在生态和细胞水平上的障碍。所需的组织标本以前是在德国“啮齿动物传播病原体”网络的活动框架内收集的，可以用于预期的实验。对实地材料的研究将提供有关自然界中汉坦病毒溢出感染的发生、频率和致病后果的原始数据。平行进行的体外实验将重点放在受体分子和先天免疫成分上，作为汉坦病毒宿主范围的预期分子决定因素。该方法包括对自然汉坦病毒宿主的基因组和转录组进行具体分析。为了进一步确定在细胞水平上决定物种屏障的因素，这些有针对性的调查将与受感染的啮齿动物来源细胞的比较转录组分析相结合，作为一种开放的策略。综上所述，拟议的独特的生态实地研究与最新的分子和病毒学研究相结合，是第一个关注汉坦病毒溢出感染的综合研究。已建立的工具和获得的数据不仅将使人们能够对汉坦病毒的物种障碍有价值的洞察，还可能大大促进啮齿动物传播病原体的一般领域的发展。该项目将在申请者的长期互动中进行，包括对博士生的联合监督。此外，还将在优先方案范围内与其他项目伙伴交流想法、方法和标本。

Hantaviruses (Bunyaviridae family), emerging viruses causing two human zoonoses, hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome, are well known for their strict association with their reservoir hosts, mainly rodents. However, so called spillover infections of non-reservoir animals occur in nature and might provide crucial insights into the mechanisms of hantavirus species barriers and processes of the virus host switch. This proposal is focused on comparative analyses of natural and spillover infections of the three hantaviruses present in Germany; Puumala virus (PUUV) carried by bank vole (Myodes glareolus), Dobrava-Belgrade virus (DOBV) carried by the striped field mouse (Apodemus agrarius), and Tula virus (TULV) carried by the common vole (Microtus arvalis) and related Microtus species.The combination of studies on syntopically occurring rodent species (including reservoir and non-reservoir species) and in vitro experiments will allow studying the host species barriers on the ecological as well as cellular level. The required tissue specimens were collected before in frame of the activities of the German network “„Rodent-borne pathogens“ and can be used for the desired experiments. Studies of field materials will provide original data on occurrence, frequency, and pathogenetic consequences of hantavirus spillover infections in nature. In vitro experiments conducted in parallel will focus on receptor molecules and innate immunity components as anticipated molecular determinants of the hantavirus host range. The approach includes a specific analysis of the genome and transcriptome of natural hantavirus hosts. In order to identify further factors determining the species barrier on the cellular level, these targeted investigations will be combined with comparative transcriptome analysis of the infected rodent-derived cells as an “open view” strategy.In summary, the proposed unique combination of ecologic field studies with state-of-theart molecular and virological investigations represents the first comprehensive study focusing on hantavirus spillover infections. The established tools and obtained data will not only allow valuable insights into the hantavirus species barriers but might also significantly advance the field of rodent-borne pathogens in general.The project will be performed in permanent interaction of the applicants which includes joint supervision of the Ph.D. students. In addition, an exchange of ideas, methods, and specimens will be established with other project partners within the Priority Programme.