Animal models of emerging tick-borne phleboviruses: Determining target cells in a lethal model of SFTSV infection

Keita Matsuno, Yasuko Orba, Kimberly Maede-White, Dana Scott, Friederike Feldmann, Mifang Liang, Hideki Ebihara

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Article number104
JournalFrontiers in Microbiology
Volume8
Issue numberJAN
DOIs
StatePublished - Jan 30 2017

Fingerprint

Phlebovirus
Ticks
Virus Diseases
Thrombocytopenia
Fever
Animal Models
Viruses
Lymphopenia
Spleen
Lymph Nodes
Macrophages
Interferon Receptors
B-Lymphoid Precursor Cells
Macaca
Infection
Knockout Mice
B-Lymphocytes
Necrosis
Kidney

Keywords

  • Aged mouse
  • Disease modeling
  • Heartland virus
  • Immunocompromised mouse
  • Mouse
  • Nonhuman primate
  • Severe fever with thrombocytopenia syndrome virus

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

Animal models of emerging tick-borne phleboviruses : Determining target cells in a lethal model of SFTSV infection. / Matsuno, Keita; Orba, Yasuko; Maede-White, Kimberly; Scott, Dana; Feldmann, Friederike; Liang, Mifang; Ebihara, Hideki.

In: Frontiers in Microbiology, Vol. 8, No. JAN, 104, 30.01.2017.

Research output: Contribution to journalArticle

Matsuno, Keita ; Orba, Yasuko ; Maede-White, Kimberly ; Scott, Dana ; Feldmann, Friederike ; Liang, Mifang ; Ebihara, Hideki. / Animal models of emerging tick-borne phleboviruses : Determining target cells in a lethal model of SFTSV infection. In: Frontiers in Microbiology. 2017 ; Vol. 8, No. JAN.
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