Vascular Leak and Hypercytokinemia Associated with Severe Fever with Thrombocytopenia Syndrome Virus Infection in Mice
by
Jonna B. Westover 1,†, Brady T. Hickerson 1,†
, Arnaud J. Van Wettere 1,2, Brett L. Hurst 1, Jacqueline P. Kurz 1,2, Ashley Dagley 1, Petra Wülfroth 3, Takashi Komeno 4, Yousuke Furuta 4, Thomas Steiner 3 and Brian B. Gowen 1,*
Jonna B. Westover 1,†, Brady T. Hickerson 1,†, Arnaud J. Van Wettere 1,2, Brett L. Hurst 1, Jacqueline P. Kurz 1,2, Ashley Dagley 1, Petra Wülfroth 3, Takashi Komeno 4, Yousuke Furuta 4, Thomas Steiner 3 and Brian B. Gowen 1,*
1
Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT 84322, USA
2
Utah Veterinary Diagnostic Laboratory, Utah State University, Logan, UT 84341, USA
3
MChE-Trading Handels-GmbH, Vienna 1060, Austria
4
FUJIFILM Toyama Chemical Co., Ltd., Toyama 930-8508, Japan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pathogens 2019, 8(4), 158; https://doi.org/10.3390/pathogens8040158
Received: 19 August 2019 / Revised: 18 September 2019 / Accepted: 19 September 2019 / Published: 21 September 2019
(This article belongs to the Special Issue Comparative Animal Models of Human Viral Infections)
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever (VHF) endemic to China, South Korea, Japan, and Vietnam. Here we characterize the pathogenesis and natural history of disease in IFNAR-/- mice challenged with the HB29 strain of SFTS virus (SFTSV) and demonstrate hallmark features of VHF such as vascular leak and high concentrations of proinflammatory cytokines in blood and tissues. Treatment with FX06, a natural plasmin digest product of fibrin in clinical development as a treatment for vascular leak, reduced vascular permeability associated with SFTSV infection but did not significantly improve survival outcome. Further studies are needed to assess the role of vascular compromise in the SFTS disease process modeled in IFNAR-/- mice.
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Keywords:
severe fever with thrombocytopenia syndrome; Huaiyangshan banyangvirus; viral hemorrhagic fever; vascular leak; cytokine storm
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MDPI and ACS Style
Westover, J.B.; Hickerson, B.T.; Van Wettere, A.J.; Hurst, B.L.; Kurz, J.P.; Dagley, A.; Wülfroth, P.; Komeno, T.; Furuta, Y.; Steiner, T.; Gowen, B.B. Vascular Leak and Hypercytokinemia Associated with Severe Fever with Thrombocytopenia Syndrome Virus Infection in Mice. Pathogens 2019, 8, 158.
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