Hantaviruses: crossing the species barrier of natural hosts

汉坦病毒：跨越自然宿主的物种屏障

• 批准号: 226336313
• 负责人: Professor Dr. Detlev H. Krüger
• 金额: --
• 依托单位: Institut für Neue und Neuartige Tierseuchenerreger (INNT)
• 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 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/226336313?language=en
• 关键词: Hantaviruses; crossing; species; barrier; natural

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.

汉坦病毒属布尼亚病毒科（Bunyaviridae），是引起肾综合征出血热（Hemorrhagic Fever with Renal Syndrome）和汉坦病毒心肺综合征（Hantavirus Cardiopulmonary Syndrome）两种人畜共患病的新型病毒。然而，所谓的溢出感染的非水库动物发生在自然界中，并可能提供重要的见解汉坦病毒的种属屏障和过程中的病毒宿主转换的机制。这项建议的重点是对德国存在的三种汉他病毒的自然感染和外溢感染进行比较分析;库田鼠携带的普马拉病毒（PUUV）（Myodes glareolus），由条纹田鼠携带的多布拉瓦-贝尔格莱德病毒（DOBV）（黑线姬鼠），和由普通田鼠携带的图拉病毒（TULV）（Microtus arvalis）和相关的田鼠物种。对共点发生啮齿动物物种的研究的结合（包括宿主和非宿主物种）和体外实验将允许在生态和细胞水平上研究宿主物种屏障。所需的组织标本是在德国网络“啮齿动物传播的病原体”活动框架内收集的，可用于所需的实验。野外资料的研究将提供关于汉坦病毒在自然界中外溢感染的发生、频率和致病后果的原始数据。平行进行的体外实验将集中在受体分子和先天免疫组分作为汉坦病毒宿主范围的预期分子决定因素。该方法包括对天然汉坦病毒宿主的基因组和转录组的特异性分析。为了确定进一步的因素，确定在细胞水平上的物种屏障，这些有针对性的调查将结合比较转录组分析的感染啮齿类动物衍生的细胞作为一个“开放的观点”strategy.In总结，提出了独特的结合生态领域的研究与国家的最先进的分子和病毒学的调查代表了第一个全面的研究集中在汉坦病毒溢出感染。已建立的工具和获得的数据不仅可以对汉坦病毒物种屏障进行有价值的深入了解，而且还可能显著推进啮齿动物传播病原体领域的发展。学生此外，还将与优先计划内的其他项目合作伙伴交流想法、方法和标本。

项目成果

Revised time scales of RNA virus evolution based on spatial information

• DOI: 10.1098/rspb.2017.0857
• 发表时间: 2017-08-16
• 期刊: PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
• 影响因子: 4.7
• 作者: Saxenhofer, Moritz;de Melo, Vanessa Weber;Heckel, Gerald
• 通讯作者: Heckel, Gerald

High genetic structuring of Tula hantavirus

• DOI: 10.1007/s00705-016-2762-6
• 发表时间: 2016-05-01
• 期刊: ARCHIVES OF VIROLOGY
• 影响因子: 2.7
• 作者: Schmidt, Sabrina;Saxenhofer, Moritz;Ulrich, Rainer G.
• 通讯作者: Ulrich, Rainer G.

Phylogenetic analysis of Puumala virus strains from Central Europe highlights the need for a full-genome perspective on hantavirus evolution

对来自中欧的普马拉病毒株的系统发育分析凸显了对汉坦病毒进化进行全基因组视角的必要性

• DOI: 10.1007/s11262-017-1484-5
• 发表时间: 2017
• 期刊: Virus Genes
• 影响因子: 1.6
• 作者: Szabó R;Radosa L;Ličková M;Sláviková M;Heroldová M;Stanko M;Pejčoch M;Osterberg A;Laenen L;Schex S;Ulrich RG;Essbauer S;Maes P;Klempa B
• 通讯作者: Klempa B

Autochthonous Dobrava-Belgrade virus infection in Eastern Germany.

德国东部本土多布拉瓦-贝尔格莱德病毒感染

• DOI: 10.5414/cn108192
• 发表时间: 2015
• 期刊: Clinical nephrology
• 影响因子: 1.1
• 作者: Rasche FM;Schmidt S;Kretzschmar C;Mertens M;Thiel J;Groschup MH;Schlegel M;Mayer C;Lindner TH;Schiekofer S;Ulrich RG
• 通讯作者: Ulrich RG

A highly divergent Puumala virus lineage in southern Poland

• DOI: 10.1007/s00705-016-3200-5
• 发表时间: 2017-05-01
• 期刊: ARCHIVES OF VIROLOGY
• 影响因子: 2.7
• 作者: Rosenfeld, Ulrike M.;Drewes, Stephan;Ulrich, Rainer G.
• 通讯作者: Ulrich, Rainer G.