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

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 repl...

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Autores principales: Strandin, Tomas, Smura, Teemu, Ahola, Paula, Aaltonen, Kirsi, Sironen, Tarja, Hepojoki, Jussi, Eckerle, Isabella, Ulrich, Rainer G., Vapalahti, Olli, Kipar, Anja, Forbes, Kristian M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232471/
https://www.ncbi.nlm.nih.gov/pubmed/32316667
http://dx.doi.org/10.3390/v12040457
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author Strandin, Tomas
Smura, Teemu
Ahola, Paula
Aaltonen, Kirsi
Sironen, Tarja
Hepojoki, Jussi
Eckerle, Isabella
Ulrich, Rainer G.
Vapalahti, Olli
Kipar, Anja
Forbes, Kristian M.
author_facet Strandin, Tomas
Smura, Teemu
Ahola, Paula
Aaltonen, Kirsi
Sironen, Tarja
Hepojoki, Jussi
Eckerle, Isabella
Ulrich, Rainer G.
Vapalahti, Olli
Kipar, Anja
Forbes, Kristian M.
author_sort Strandin, Tomas
collection PubMed
description 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.
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spelling pubmed-72324712020-05-22 Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties Strandin, Tomas Smura, Teemu Ahola, Paula Aaltonen, Kirsi Sironen, Tarja Hepojoki, Jussi Eckerle, Isabella Ulrich, Rainer G. Vapalahti, Olli Kipar, Anja Forbes, Kristian M. Viruses Article 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. MDPI 2020-04-17 /pmc/articles/PMC7232471/ /pubmed/32316667 http://dx.doi.org/10.3390/v12040457 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Strandin, Tomas
Smura, Teemu
Ahola, Paula
Aaltonen, Kirsi
Sironen, Tarja
Hepojoki, Jussi
Eckerle, Isabella
Ulrich, Rainer G.
Vapalahti, Olli
Kipar, Anja
Forbes, Kristian M.
Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties
title Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties
title_full Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties
title_fullStr Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties
title_full_unstemmed Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties
title_short Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties
title_sort orthohantavirus isolated in reservoir host cells displays minimal genetic changes and retains wild-type infection properties
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232471/
https://www.ncbi.nlm.nih.gov/pubmed/32316667
http://dx.doi.org/10.3390/v12040457
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