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

SJ Park, YI Kim, A Park, HI Kwon, EH Kim, YJ Si… - Nature …, 2019 - nature.com
SJ Park, YI Kim, A Park, HI Kwon, EH Kim, YJ Si, MS Song, CH Lee, K Jung, WJ Shin, J Zeng…
Nature microbiology, 2019nature.com
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~ 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 …
Abstract
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 ~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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