Su-Jin Parka,b, Young-Il Kima,b, Angela Parkc, Hyeok-Il Kwona,b, Eun-Ha Kima,b, Young-Jae Sia,b, Min-Suk Songa,b, Chul-Ho Leed, Kyle Jungc, Woo-Jin Shinc, Jianxiong Zengc, Younho Choic, Jae U. Jungc,* & Young Ki Choia,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.
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.