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충북대학교 의과대학

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Nat. Microbiol., March 2019, 4, pages438-446 | DOI https://doi.org/10.1038/s41564-018-0317-1 Ferret animal model of severe fever with thrombocytopenia syndrome phlebovirus for human lethal infection and pathogenesis.

Su-Jin Park^a,b, Young-Il Kim^a,b, Angela Park^c, Hyeok-Il Kwon^a,b, Eun-Ha Kim^a,b, Young-Jae Si^a,b, Min-Suk Song^a,b, Chul-Ho Lee^d, Kyle Jung^c, Woo-Jin Shin^c, Jianxiong Zeng^c, Younho Choi^c, Jae U. Jung^c,* & Young Ki Choi^a,b,*

^aDepartment of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea
^bZoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Republic of Korea
^cDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
^dLaboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon, Republic of Korea

These authors contributed equally: Su-Jin Park, Young-Il Kim.

^*Correspondence to Jae U. Jung or Young Ki Choi.

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.

논문정보

형식Research article
게재일2019년 03월 (BRIC 등록일 2019-09-10)
연구진국내(교신)+국외 연구진
분야 의약학 > 감염의학

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