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Open AccessArticle

Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties

Zoonosis Unit, Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, Finland
Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, 00790 Helsinki, Finland
Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
Institute of Virology, University of Bonn Medical Centre, 53012 Bonn, Germany
Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany
Department of Biological Sciences, University of Arkansas, Fayetteville, NC 72701, USA
Author to whom correspondence should be addressed.
Current address: Geneva Centre for Emerging Viral Diseases, University Hospital of Geneva & Department of Microbiology and Molecular Medicine, University of Geneva, 1205 Geneva, Switzerland.
Viruses 2020, 12(4), 457;
Received: 16 March 2020 / Revised: 12 April 2020 / Accepted: 13 April 2020 / Published: 17 April 2020
(This article belongs to the Special Issue Virus Ecology and Evolution: Current Research and Future Directions)
Orthohantaviruses are globally emerging zoonotic pathogens. While the reservoir host role of several rodent species is well-established, detailed research on the mechanisms of host-othohantavirus interactions has been constrained by the lack of an experimental system that is able to effectively replicate natural infections in controlled settings. Here we report the isolation, and genetic and phenotypic characterization of a novel Puumala orthohantavirus (PUUV) in cells derived from its reservoir host, the bank vole. The isolation process resulted in cell culture infection that evaded antiviral responses, persisted cell passaging, and had minor viral genome alterations. Critically, experimental infections of bank voles with the new isolate resembled natural infections in terms of viral load and host cell distribution. When compared to an attenuated Vero E6 cell-adapted PUUV Kazan strain, the novel isolate demonstrated delayed virus-specific humoral responses. A lack of virus-specific antibodies was also observed during experimental infections with wild-type PUUV, suggesting that delayed seroconversion could be a general phenomenon during orthohantavirus infection in reservoir hosts. Our results demonstrate that orthohantavirus isolation on cells derived from a vole reservoir host retains wild-type infection properties and should be considered the method of choice for experimental infection models to replicate natural processes. View Full-Text
Keywords: immunity; Puumala orthohantavirus; rodent reservoir; spillover; vole; zoonoses immunity; Puumala orthohantavirus; rodent reservoir; spillover; vole; zoonoses
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Strandin, T.; Smura, T.; Ahola, P.; Aaltonen, K.; Sironen, T.; Hepojoki, J.; Eckerle, I.; Ulrich, R.G.; Vapalahti, O.; Kipar, A.; Forbes, K.M. Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties. Viruses 2020, 12, 457.

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