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

• DOI: 10.1128/jvi.01727-24
• Publication Date: 2024-12-31T13:43:14Z
• Authors: Zi-Yun Chen; Jie Zhang; Pei-Jun He; Tao Xiong; Dai-Yun Zhu; Wen-Jie Zhu; Xue-Bing Ni; Li-Feng Du; Qian Wang; Ya-Wei Zhang; Luo-Yuan Xia; Dong-Sheng Chen; Liang-Jing Li; Ming-Zhu Zhang; Xiao Ming Cui; Tian-Hong Wang; Juan Wang; Zhenfei Wang; Tian-Feng An; Wu-Chun Cao; Xiao-Hua Liu; En-Jiong Huang; Na Jia
• Keywords: Ixodes persulcatus; Infectivity

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, group deubiquinylases (DUBs), disrupt innate immune response. Yezo virus (YEZV), recently discovered pathogenic orthonairovirus, was first reported in Japan 2021. In this study, we successfully isolated and identified YEZV new Jiànchuān tick (JCTV), from Ixodes persulcatus Haemaphysalis montgomeryi ticks, respectively, China. We found that vOTU domains JCTV exhibited both DUB deISGylase activities, though potentially less broad deISGylation compared to Crimean-Congo hemorrhagic fever (CCHFV) during natural infection. Phylogenetic analysis including 83 sequences, revealed high diversity domain. Interestingly, retrospective screening tick-bite patients 2012 2016 northeastern China traced as far back 2012, identifying four cases. Additionally, primarily infected I. (31.4%) Dermacentor nuttalli (10.5%) northern China, while infection rates H. (81.3%) southern summary, our work emphasizes active surveillance imperative need for development domain-targeted anti-virals, offering potential therapeutic solutions spectrum IMPORTANCE The DUBs, mimic functions host DUBs enhance infectivity may serve drug targets. vOTUs different orthonairoviruses exhibit distinct preferences toward ubiquitin (Ub) ubiquitin-like protein interferon stimulated gene 15 (ISG15). investigated deubiquitinase various orthonairoviral using an overexpression system vitro . Our findings illustrate can cleave Ub ISG15 system, but these viruses narrower capacity than CCHFV This suggests have relationship pathogenesis.