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

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

Author information

1
Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA.
2
Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA; Utah Veterinary Diagnostic Laboratory, 950 E. 1400 N., Logan, UT 84341, USA.
3
Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA; Zhengzhou University, 100 Kexue Ave., Zhengzhou Shi, Henan Sheng, People's Republic of China.
4
University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA.
5
Utah Veterinary Diagnostic Laboratory, 950 E. 1400 N., Logan, UT 84341, USA.
6
Research Laboratories, Toyama Chemical Co., Ltd., Toyama 930-8508, Japan.
7
Utah State University, 5600 Old Main Hill, Logan, UT 84322, USA. Electronic address: brian.gowen@usu.edu.

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.

KEYWORDS:

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

PMID:
28865344
PMCID:
PMC5623653
DOI:
10.1016/j.virol.2017.08.004
[Indexed for MEDLINE]
Free PMC Article

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