Heartland virus infection in hamsters deficient in type I interferon signaling: Protracted disease course ameliorated by favipiravir

Jonna B. Westover, Johanna D. Rigas, Arnaud J. Van Wettere, Rong Li, Brady T. Hickerson, Kie Hoon Jung, Jinxin Miao, Erin S. Reynolds, Bettina L. Conrad, Skot Nielson, Yousuke Furuta, Saravanan Thangamani, Zhongde Wang, Brian B. Gowen

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Heartland virus (HRTV) is an emerging tick-borne virus (Bunyaviridae, Phlebovirus) that has caused sporadic cases of human disease in several central and mid-eastern states of America. Animal models of HRTV disease are needed to gain insights into viral pathogenesis and advancing antiviral drug development. Presence of clinical disease following HRTV challenge in hamsters deficient in STAT2 function underscores the important role played by type I interferon-induced antiviral responses. However, the recovery of most of the infected animals suggests that other mechanisms to control infection and limit disease offer substantial protection. The most prominent disease sign with HRTV infection in STAT2 knockout hamsters was dramatic weight loss with clinical laboratory and histopathology demonstrating acute inflammation in the spleen, lymph node, liver and lung. Finally, we show that HRTV disease in hamsters can be prevented by the use of favipiravir, a promising broad-spectrum antiviral in clinical development for the treatment of influenza.

Original languageEnglish (US)
Pages (from-to)175-183
Number of pages9
JournalVirology
Volume511
DOIs
StatePublished - Nov 1 2017

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Keywords

  • Animal model
  • Favipiravir
  • Heartland virus
  • Phlebovirus
  • Severe fever with thrombocytopenia syndrome virus
  • Type I interferon

ASJC Scopus subject areas

  • Virology

Cite this

Westover, J. B., Rigas, J. D., Van Wettere, A. J., Li, R., Hickerson, B. T., Jung, K. H., Miao, J., Reynolds, E. S., Conrad, B. L., Nielson, S., Furuta, Y., Thangamani, S., Wang, Z., & Gowen, B. B. (2017). Heartland virus infection in hamsters deficient in type I interferon signaling: Protracted disease course ameliorated by favipiravir. Virology, 511, 175-183. https://doi.org/10.1016/j.virol.2017.08.004