Pathogenesis of Rift Valley Fever Virus Aerosol Infection in <i>STAT2</i> Knockout Hamsters

Rift Valley fever virus (RVFV) is an emerging pathogen capable of causing severe disease in livestock and humans and can be transmitted by multiple routes including aerosol exposure. Several animal models have been developed to gain insight into the pathogenesis associated with aerosolized RVFV infe...

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Main Authors: Brady T. Hickerson, Jonna B. Westover, Arnaud J. Van Wettere, Johanna D. Rigas, Jinxin Miao, Bettina L. Conrad, Neil E. Motter, Zhongde Wang, Brian B. Gowen
Format: Article
Language:English
Published: MDPI AG 2018-11-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/10/11/651
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author Brady T. Hickerson
Jonna B. Westover
Arnaud J. Van Wettere
Johanna D. Rigas
Jinxin Miao
Bettina L. Conrad
Neil E. Motter
Zhongde Wang
Brian B. Gowen
author_facet Brady T. Hickerson
Jonna B. Westover
Arnaud J. Van Wettere
Johanna D. Rigas
Jinxin Miao
Bettina L. Conrad
Neil E. Motter
Zhongde Wang
Brian B. Gowen
author_sort Brady T. Hickerson
collection DOAJ
description Rift Valley fever virus (RVFV) is an emerging pathogen capable of causing severe disease in livestock and humans and can be transmitted by multiple routes including aerosol exposure. Several animal models have been developed to gain insight into the pathogenesis associated with aerosolized RVFV infection, but work with these models is restricted to high containment biosafety level (BSL) laboratories limiting their use for antiviral and vaccine development studies. Here, we report on a new RVFV inhalation infection model in <i>STAT2</i> KO hamsters exposed to aerosolized MP-12 vaccine virus by nose-only inhalation that enables a more accurate delivery and measurement of exposure dose. RVFV was detected in hepatic and other tissues 4&#8315;5 days after challenge, consistent with virus-induced lesions in the liver, spleen and lung. Furthermore, assessment of blood chemistry and hematological parameters revealed alterations in several liver disease markers and white blood cell parameters. Our results indicate that <i>STAT2</i> KO hamsters develop a disease course that shares features of disease observed in human cases and in other animal models of RVFV aerosol exposure, supporting the use of this BSL-2 infection model for countermeasure development efforts.
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spelling doaj.art-01331e20e29e452abba7fecf6a5fad842022-12-21T17:26:27ZengMDPI AGViruses1999-49152018-11-01101165110.3390/v10110651v10110651Pathogenesis of Rift Valley Fever Virus Aerosol Infection in <i>STAT2</i> Knockout HamstersBrady T. Hickerson0Jonna B. Westover1Arnaud J. Van Wettere2Johanna D. Rigas3Jinxin Miao4Bettina L. Conrad5Neil E. Motter6Zhongde Wang7Brian B. Gowen8Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USADepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USADepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USAUtah Veterinary Diagnostic Laboratory, Logan, UT 84341, USADepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USAUtah Veterinary Diagnostic Laboratory, Logan, UT 84341, USADepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USADepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USADepartment of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USARift Valley fever virus (RVFV) is an emerging pathogen capable of causing severe disease in livestock and humans and can be transmitted by multiple routes including aerosol exposure. Several animal models have been developed to gain insight into the pathogenesis associated with aerosolized RVFV infection, but work with these models is restricted to high containment biosafety level (BSL) laboratories limiting their use for antiviral and vaccine development studies. Here, we report on a new RVFV inhalation infection model in <i>STAT2</i> KO hamsters exposed to aerosolized MP-12 vaccine virus by nose-only inhalation that enables a more accurate delivery and measurement of exposure dose. RVFV was detected in hepatic and other tissues 4&#8315;5 days after challenge, consistent with virus-induced lesions in the liver, spleen and lung. Furthermore, assessment of blood chemistry and hematological parameters revealed alterations in several liver disease markers and white blood cell parameters. Our results indicate that <i>STAT2</i> KO hamsters develop a disease course that shares features of disease observed in human cases and in other animal models of RVFV aerosol exposure, supporting the use of this BSL-2 infection model for countermeasure development efforts.https://www.mdpi.com/1999-4915/10/11/651Rift Valley fever virusbunyavirusphlebovirusaerosol<i>STAT2</i>interferon
spellingShingle Brady T. Hickerson
Jonna B. Westover
Arnaud J. Van Wettere
Johanna D. Rigas
Jinxin Miao
Bettina L. Conrad
Neil E. Motter
Zhongde Wang
Brian B. Gowen
Pathogenesis of Rift Valley Fever Virus Aerosol Infection in <i>STAT2</i> Knockout Hamsters
Viruses
Rift Valley fever virus
bunyavirus
phlebovirus
aerosol
<i>STAT2</i>
interferon
title Pathogenesis of Rift Valley Fever Virus Aerosol Infection in <i>STAT2</i> Knockout Hamsters
title_full Pathogenesis of Rift Valley Fever Virus Aerosol Infection in <i>STAT2</i> Knockout Hamsters
title_fullStr Pathogenesis of Rift Valley Fever Virus Aerosol Infection in <i>STAT2</i> Knockout Hamsters
title_full_unstemmed Pathogenesis of Rift Valley Fever Virus Aerosol Infection in <i>STAT2</i> Knockout Hamsters
title_short Pathogenesis of Rift Valley Fever Virus Aerosol Infection in <i>STAT2</i> Knockout Hamsters
title_sort pathogenesis of rift valley fever virus aerosol infection in i stat2 i knockout hamsters
topic Rift Valley fever virus
bunyavirus
phlebovirus
aerosol
<i>STAT2</i>
interferon
url https://www.mdpi.com/1999-4915/10/11/651
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