A Model for the Production of Regulatory Grade Viral Hemorrhagic Fever Exposure Stocks: From Field Surveillance to Advanced Characterization of SFTSV

Viruses. 2020 Aug 29;12(9):958. doi: 10.3390/v12090958.

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging human pathogen, endemic in areas of China, Japan, and the Korea (KOR). It is primarily transmitted through infected ticks and can cause a severe hemorrhagic fever disease with case fatality rates as high as 30%. Despite its high virulence and increasing prevalence, molecular and functional studies in situ are scarce due to the limited availability of high-titer SFTSV exposure stocks. During the course of field virologic surveillance in 2017, we detected SFTSV in ticks and in a symptomatic soldier in a KOR Army training area. SFTSV was isolated from the ticks producing a high-titer viral exposure stock. Through the use of advanced genomic tools, we present here a complete, in-depth characterization of this viral stock, including a comparison with both the virus in its arthropod source and in the human case, and an in vivo study of its pathogenicity. Thanks to this detailed characterization, this SFTSV viral exposure stock constitutes a quality biological tool for the study of this viral agent and for the development of medical countermeasures, fulfilling the requirements of the main regulatory agencies.

Keywords: Bunyavirales; IFNAR-/- mice Phenuiviridae; SFTS; SFTSV; bandavirus; bunyavirus; field virologic surveillance; phenuivirus; severe fever with thrombocytopenia syndrome; severe fever with thrombocytopenia syndrome virus; target-enrichment high-throughput sequencing; tick borne virus infection; viral hemorrhagic fever; virus exposure stock.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Bunyaviridae Infections / genetics
  • Bunyaviridae Infections / metabolism
  • Bunyaviridae Infections / virology*
  • Female
  • Genome, Viral
  • Hemorrhagic Fevers, Viral / virology*
  • Humans
  • Male
  • Mice
  • Phlebovirus / isolation & purification*
  • Phlebovirus / physiology
  • Phylogeny
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / metabolism
  • Republic of Korea
  • Ticks / virology

Substances

  • Receptor, Interferon alpha-beta