Characteristics of viral ovarian tumor domain protease from two emerging orthonairoviruses and identification of Yezo virus human infections in northeastern China as early as 2012

作者：Zi-Yun Chen, Jie Zhang, Pei-Jun He, Tao Xiong, Dai-Yun Zhu, Wen-Jie Zhu, Xue-Bing Ni, Li-Feng Du, Qian Wang, Yawei Zhang, Luo‐Yuan Xia, Dongsheng Chen, Liangjing Li, Mingzhu Zhang, Xiao Ming Cui, Tianhong Wang, Juan Wang, Zhenfei Wang, Tian-Feng An, Wu‐Chun Cao, Xiao-Hua Liu, En-Jiong Huang, Na Jia · 发表于：Journal of Virology · 年份：2024 · DOI：10.1128/jvi.01727-24 · 被引用次数：9 · 研究领域：Viral Infections and Vectors、Vector-Borne Animal Diseases、Mosquito-borne diseases and control

ABSTRACT Emerging tick-borne orthonairovirus infections pose a growing global concern, with limited understanding of the viral ovarian tumor-like cysteine proteases (vOTUs) encoded by novel orthonairoviruses. These vOTUs, a group of deubiquinylases (DUBs), disrupt the innate immune response. Yezo virus (YEZV), a recently discovered pathogenic orthonairovirus, was first reported in Japan in 2021. In this study, we successfully isolated and identified YEZV and a new orthonairovirus, Jiànchuān tick virus (JCTV), from Ixodes persulcatus and Haemaphysalis montgomeryi ticks, respectively, in China. We found that the vOTU domains encoded by YEZV and JCTV exhibited both DUB and deISGylase activities, though with potentially less broad deISGylation compared to that of Crimean-Congo hemorrhagic fever virus (CCHFV) during natural infection. Phylogenetic analysis of global vOTUs, including 83 new sequences, revealed a high diversity of this domain. Interestingly, retrospective screening of tick-bite patients from 2012 to 2016 in northeastern China traced YEZV infections as far back as 2012, identifying four cases. Additionally, YEZV primarily infected I. persulcatus (31.4%) and Dermacentor nuttalli (10.5%) in northern China, while JCTV exhibited high infection rates in H. montgomeryi (81.3%) in southern China. In summary, our work emphasizes the active surveillance of orthonairovirus infections and the imperative need for the development of vOTU domain-targeted anti-virals, offering pote...