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

Virology. 2017 Nov;511:175-183. doi: 10.1016/j.virol.2017.08.004. Epub 2017 Aug 31.


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.

Keywords: Animal model; Favipiravir; Heartland virus; Phlebovirus; Severe fever with thrombocytopenia syndrome virus; Type I interferon.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / therapeutic use*
  • Animal Structures / pathology
  • Animals
  • Antiviral Agents / therapeutic use*
  • Bunyaviridae Infections / pathology*
  • Bunyaviridae Infections / prevention & control*
  • Chemoprevention
  • Cricetinae
  • Disease Models, Animal
  • Inflammation / pathology
  • Interferon Type I / immunology
  • Pyrazines / therapeutic use*
  • STAT2 Transcription Factor / deficiency*
  • Treatment Outcome


  • Amides
  • Antiviral Agents
  • Interferon Type I
  • Pyrazines
  • STAT2 Transcription Factor
  • Stat2 protein, mouse
  • favipiravir