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Wild Mice and Shrews as Natural Reservoirs of Emerging Tickborne Yezo Virus, Hokkaido, Japan, 2023–2025

Wild Mice and Shrews as Natural Reservoirs of Emerging Tickborne Yezo Virus, Hokkaido, Japan, 2023–2025

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Wild Mice and Shrews as Natural Reservoirs of Emerging Tickborne Yezo Virus, Hokkaido, Japan, 2023–2025

A-Z Index × Submit A-Z Index × Submit A-Z Index Search Dropdown × Submit Facebook Twitter LinkedIn Syndicate Emerging Infectious Disease journal ISSN: 1080-6059 Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.

We screened 420 wild small mammals and 2,273 ticks for infections with an emerging tickborne orthonairovirus, Yezo virus, during 2023–2025 in Hokkaido, Japan. We detected virus in mice, shrews, and ticks that were closely related. Apodemus spp. mice and Sorex spp. shrews were identified as potent natural reservoirs of Yezo virus.

Yezo virus (YEZV) is an emerging tickborne orthonairovirus initially identified in febrile patients after a tick bite in Hokkaido, Japan ( 1 ). Since the first report in 2021, YEZV infections in humans have been reported from Hokkaido, northeastern China, and Russia ( 2 – 5 ). Despite its public health significance, our understanding of YEZV circulation in nature remains limited. In previous studies ( 1 , 6 , 7 ), we demonstrated that raccoons ( Procyon lotor ), tanukis ( Nyctereutes procyonoides ), and sika deer ( Cervus nippon ) possess antibodies against YEZV, suggesting YEZV circulation in the field. However, the vertebrate reservoirs remain unidentified. In contrast, among several tick species in YEZV-endemic regions, Ixodes spp. ticks are suspected to play crucial roles in the pathogen’s circulation and transmission to humans ( 3 , 7 – 9 ). Given that larval and nymphal Ixodes spp. ticks mainly infest small mammals in Hokkaido ( 10 ), we hypothesized that those animals serve as natural reservoir hosts of YEZV. This study reports YEZV infection status and the phylogenetic relationships of YEZV in 3 taxonomic groups of native small mammals in Hokkaido: mice (order Rodentia, family Muridae, genus Apodemus ), voles (order Rodentia, family Cricetidae, genus Craseomys and Clethrionomys ), and shrews (order Eulipotyphla, family Soricidae, genus Sorex ) ( 11 , 12 ).

We captured small mammals at 14 sites across Hokkaido in 2023 and 2025 ( Appendix Figure). We identified the species of animal on the basis of morphologic features ( 11 ) and confirmed species by sequencing the mitochondrial genome (data not shown). We collected liver, spleen, lung, heart, kidney, brain, and serum samples of trapped animals. All animal experiments were approved by the Animal Care and Use Committee of Hokkaido University (approval nos. 23-0063, 23–0178, and 25-0119). Permission to capture wild mammals was obtained from the Hokkaido Government.

We captured a total of 420 wild small mammals, consisting of 252 mice ( Apodemus argenteus and A. speciosus ), 121 voles ( Craseomys rufocanus and Clethrionomys rutilus ), and 47 shrews ( Sorex caecutiens , S. gracillimus , and S. unguiculatus ). We collected serum samples from 199 animals and screened them for YEZV-specific antibodies by ELISA ( 1 ). Of the 199 serum samples, 14 (7.0%) samples were positive for YEZV antibodies ( Table 1 ). The seroprevalence was not statistically different between mice and voles (p = 0.561 by Fisher exact test). We screened liver samples from all 420 animals for YEZV small (S) segment RNA using real-time quantitative reverse transcription PCR (qRT-PCR) ( 8 ). We detected YEZV RNA in 16 samples from mice and shrews, whereas all voles tested negative ( Table 1 ). RNA detection rates in mice and shrews were significantly higher than…