Hantaviruses: crossing the species barrier of natural hosts

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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.