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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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/4/457 |
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| author | Tomas Strandin Teemu Smura Paula Ahola Kirsi Aaltonen Tarja Sironen Jussi Hepojoki Isabella Eckerle Rainer G. Ulrich Olli Vapalahti Anja Kipar Kristian M. Forbes |
| author_facet | Tomas Strandin Teemu Smura Paula Ahola Kirsi Aaltonen Tarja Sironen Jussi Hepojoki Isabella Eckerle Rainer G. Ulrich Olli Vapalahti Anja Kipar Kristian M. Forbes |
| author_sort | Tomas Strandin |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T20:23:32Z |
| format | Article |
| id | doaj.art-bd082b17f3cb44a4827ba1598086f0c3 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T20:23:32Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-bd082b17f3cb44a4827ba1598086f0c32023-11-19T21:59:26ZengMDPI AGViruses1999-49152020-04-0112445710.3390/v12040457Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection PropertiesTomas Strandin0Teemu Smura1Paula Ahola2Kirsi Aaltonen3Tarja Sironen4Jussi Hepojoki5Isabella Eckerle6Rainer G. Ulrich7Olli Vapalahti8Anja Kipar9Kristian M. Forbes10Zoonosis Unit, Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, FinlandZoonosis Unit, Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, FinlandZoonosis Unit, Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, FinlandZoonosis Unit, Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, FinlandZoonosis Unit, Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, FinlandZoonosis Unit, Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, FinlandInstitute of Virology, University of Bonn Medical Centre, 53012 Bonn, GermanyInstitute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, GermanyZoonosis Unit, Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, FinlandDepartment of Basic Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, 00790 Helsinki, FinlandDepartment of Biological Sciences, University of Arkansas, Fayetteville, NC 72701, USAOrthohantaviruses 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.https://www.mdpi.com/1999-4915/12/4/457immunityPuumala orthohantavirusrodent reservoirspillovervolezoonoses |
| spellingShingle | Tomas Strandin Teemu Smura Paula Ahola Kirsi Aaltonen Tarja Sironen Jussi Hepojoki Isabella Eckerle Rainer G. Ulrich Olli Vapalahti Anja Kipar Kristian M. Forbes Orthohantavirus Isolated in Reservoir Host Cells Displays Minimal Genetic Changes and Retains Wild-Type Infection Properties Viruses immunity Puumala orthohantavirus rodent reservoir spillover vole zoonoses |
| 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 | immunity Puumala orthohantavirus rodent reservoir spillover vole zoonoses |
| url | https://www.mdpi.com/1999-4915/12/4/457 |
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