NDRV的σNS蛋白拮抗樱桃谷鸭TRIM59介导的抗病毒天然免疫反应。

The σNS protein of NDRV antagonizes TRIM59-mediated antiviral innate immune response of Cherry Valley duck.

作者信息

Wang Xiuyuan, Zhang Tingting, Lu Xiaoyu, Zhang Yirui, Tian Mingzhuo, Chen Yujing, Wang Yikun, Liu Nan, Li Shuhan, Zhang Jie, Wei Liangmeng

机构信息

Shandong Provincial Key Laboratory of Zoonoses, Sino-German Cooperative Research Centre for Zoonosis of Animal Origin of Shandong Province, College of Veterinary Medicine, Shandong Agricultural University, 61 Daizong Street, Tai'An 271018, China; Collaborative innovation center for the origin and control of emerging infectious diseases, School of Clinical and Basic Medical Sciences, Shandong First Medical University, Shandong Academy of Medical Sciences, JiNan 250024, China.

出版信息

Infect Genet Evol. 2025 Mar;128:105724. doi: 10.1016/j.meegid.2025.105724. Epub 2025 Jan 31.

DOI:10.1016/j.meegid.2025.105724

PMID:39894289

Abstract

In recent years, outbreak of the novel duck reovirus (NDRV) disease has occurred frequently in duck populations. Due to its rapid spreading, absence of effective control methods, and high treatment costs, the NDRV disease has caused huge losses to waterfowl breeding in China. As reported, four non-structural (NS) proteins are encoded by the NDRV genome, among which the σNS protein is an RNA-binding protein that can improve the stability of bound RNA by forming oligomers (Adams and Cory, 1998). Nevertheless, the mechanism by which it facilitates reovirus replication remains ambiguous. According to previous studies, the NS protein 11 of the porcine reproductive and respiratory syndrome virus (PRRSV) can interact with tripartite motif-containing 59 (TRIM59) to regulate viral infection. However, the specific role of TRIM59 in NDRV infection remains unclear. This study focused on full-length amplification of duTRIM59, the mRNA distribution of duTRIM59 in Cherry Valley duck and successive biological examinations. The homology with Anas platyrhynchos TRIM59 was 98.6 %. The mRNA distribution level of duTRIM59 showed that duTRIM59 was widely expressed in bursae and thymus of the immune organs. Nevertheless, TRIM59 comprises three domains, including the transmembrane (TM), B-box (B), and RING-finger (R) domains. It also has the activity of ubiquitin-protein ligase (E3). It has been demonstrated that NDRV replication is inhibited by TRIM59 overexpression in duck embryonic fibroblasts (DEF) cells, particularly when the R domain is intact, suggesting that the R domain plays a key role in the spreading of the NDRV virus. In contrast, NDRV infection in DEF cells increased when TRIM59 was depleted by using small interfering RNA. Moreover, the σNS protein can be co-localized with duTRIM59 and stimulate NDRV replication in DEF cells in cases of NDRV infection. This study clarifies the correlation of NDRV infection and TRIM59-mediated antiviral innate immunity, and provides a sound theoretical basis for further understanding this disease.

摘要

近年来，新型鸭呼肠孤病毒（NDRV）病在鸭群中频繁爆发。由于其传播迅速、缺乏有效的控制方法且治疗成本高，NDRV病给我国水禽养殖业造成了巨大损失。据报道，NDRV基因组编码四种非结构（NS）蛋白，其中σNS蛋白是一种RNA结合蛋白，可通过形成寡聚体来提高结合RNA的稳定性（亚当斯和科里，1998年）。然而，其促进呼肠孤病毒复制的机制仍不明确。根据以往研究，猪繁殖与呼吸综合征病毒（PRRSV）的NS蛋白11可与含三联基序的59（TRIM59）相互作用以调节病毒感染。然而，TRIM59在NDRV感染中的具体作用仍不清楚。本研究聚焦于duTRIM59的全长扩增、duTRIM59在樱桃谷鸭中的mRNA分布及后续生物学检测。其与绿头鸭TRIM59的同源性为98.6%。duTRIM59的mRNA分布水平表明，duTRIM59在免疫器官的法氏囊和胸腺中广泛表达。然而，TRIM59包含三个结构域，包括跨膜（TM）、B盒（B）和环指（R）结构域。它还具有泛素蛋白连接酶（E3）的活性。已证明在鸭胚成纤维细胞（DEF）中过表达TRIM59可抑制NDRV复制，尤其是当R结构域完整时，这表明R结构域在NDRV病毒传播中起关键作用。相反，当使用小干扰RNA使TRIM59缺失时，DEF细胞中的NDRV感染增加。此外，在NDRV感染的情况下，σNS蛋白可与duTRIM59共定位并刺激DEF细胞中的NDRV复制。本研究阐明了NDRV感染与TRIM59介导的抗病毒固有免疫的相关性，并为进一步了解该疾病提供了坚实的理论基础。