Activation of neurotoxic A1-reactive astrocytes by SFTS virus infection accelerates fatal brain damage in IFNAR1-/- mice
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초록

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach. © 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.

키워드

astrocytesCNS symptomsneuroinflammationsevere fever with thrombocytopenia syndrome (SFTS)viral infectionTHROMBOCYTOPENIA SYNDROMESEVERE FEVERPATHOGENESISINTERFERONBUNYAVIRUS
제목
Activation of neurotoxic A1-reactive astrocytes by SFTS virus infection accelerates fatal brain damage in IFNAR1-/- mice
저자
Kim, Seon-HeeChoi, Ha NyeoungJo, Min GiLee, BinaKim, Young JinSeong, HyeminSong, ChieunYoo, Han SolLee, Jeong HyunSeong, DaseulPark, Hyun-JinRoh, In-SoonYang, JinsungLee, Min YoungKim, Hye JungPark, Sang WonKim, MingyoKim, Seong JaeKim, MinkyeongKim, Hyun-JeongHong, Kyung-WookYun, Seung Pil
DOI
10.1002/jmv.29854
발행일
2024-08
유형
Article
저널명
Journal of Medical Virology
96
8