4.5 Article

Ferret animal model of severe fever with thrombocytopenia syndrome phlebovirus for human lethal infection and pathogenesis

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NATURE MICROBIOLOGY
卷 4, 期 3, 页码 438-446

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NATURE PUBLISHING GROUP
DOI: 10.1038/s41564-018-0317-1

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资金

  1. Korea Health Technology R&D Project - Ministry of Health & Welfare, Republic of Korea [HI15C2817]
  2. National Research Foundation of Korea [NRF-2017K2A9A1A01092932]
  3. National Institute of Health [AI129496, AI40718, AI140705]
  4. Ministry of Health & Welfare, Republic of Korea [HI15C2888]

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Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV), listed in the most dangerous pathogens by the World Health Organization, has 12-30% fatality rates with a characteristic thrombocytopenia syndrome. With a majority of clinically diagnosed SFTSV patients older than similar to 50 years of age, age is a critical risk factor for SFTSV morbidity and mortality. Here, we report an age-dependent ferret model of SFTSV infection and pathogenesis that fully recapitulates the clinical manifestations of human infections. Whereas young adult ferrets (<= 2 years of age) did not show any clinical symptoms and mortality, SFTSV-infected aged ferrets (>= 4 years of age) demonstrated severe thrombocytopenia, reduced white blood cell counts and high fever with 93% mortality rate. Moreover, a significantly higher viral load was observed in aged ferrets. Transcriptome analysis of SFTSV-infected young ferrets revealed strong interferon-mediated anti-viral signalling, whereas inflammatory immune responses were markedly upregulated and persisted in aged ferrets. Thus, this immunocompetent age-dependent ferret model should be useful for anti-SFTSV therapy and vaccine development.

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