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Animal Models of Emerging Tick-Borne Phleboviruses: Determining Target Cells in a Lethal Model of SFTSV Infection

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Title: Animal Models of Emerging Tick-Borne Phleboviruses: Determining Target Cells in a Lethal Model of SFTSV Infection
Authors: Matsuno, Keita Browse this author →KAKEN DB
Orba, Yasuko Browse this author →KAKEN DB
Maede-White, Kimberly Browse this author
Scott, Dana Browse this author
Feldmann, Friederike Browse this author
Liang, Mifang Browse this author
Ebihara, Hideki Browse this author
Keywords: aged mouse
disease modeling
heartland virus
immunocompromised mouse
mouse
nonhuman primate
severe fever with thrombocytopenia syndrome virus
Issue Date: 30-Jan-2017
Publisher: Frontiers Media
Journal Title: Frontiers in Microbiology
Volume: 8
Start Page: 104
Publisher DOI: 10.3389/fmicb.2017.00104
Abstract: The pathogenesis of clinical manifestations caused by newly emerging tick-borne phleboviruses [i.e., Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV)], such as severe thrombocytopenia and lymphocytopenia, are not yet fully understood. In the present study, to establish an animal model mimicking the profile of fatal human cases, we examined the susceptibilities of adult mice from 12 strains, aged mice from two strains, and cynomolgus macaques to SFTSV and/or HRTV infections. However, none of these immunocompetent animals developed lethal diseases after infection with SFTSV or HRTV. Thus, we tested a lethal animal model of SFTSV infection using interferon-α/β receptor knock-out (IFNAR-/-) mice to identify the target cell(s) of virus infection, as well as lesions that are potentially associated with hematological changes. IbaI-positive macrophages and Pax5-positive immature B cells overlapped with SFTSV-positive cells in the spleen and lymph nodes of IFNAR-/- mice, and IbaI-SFTSV-double positive cells were also observed in the liver and kidney, thereby suggesting crucial roles for macrophages in the pathogenesis of SFTSV infection in mice. In the mandibular lymph nodes and spleens of infected mice, we observed extensive necrosis comprising B220-positive B cells, which may be associated with severe lymphocytopenia. The results of this study suggest a resemblance between the IFNAR-/- mouse model and lethal infections in humans, as well as roles for multiple cells during pathogenesis in mice.
Rights: https://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/64782
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 松野 啓太

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