Novel Duck Orthoreovirus σA Protein Inhibits Interferon Signaling by Impeding STAT1/STAT2 Nuclear Translocation

IF 3 2区农林科学 Q2 INFECTIOUS DISEASES

Transboundary and Emerging Diseases Pub Date : 2025-09-15 DOI:10.1155/tbed/8440800

Boyi Xu, Chenchen Jiang, Lei Di, Lan Zhou, Zhouyuan Wang, Yi Tang, Rendong Fang, Hongzhi Wang

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Abstract

Novel duck orthoreovirus (NDRV) infection induces severe splenic necrosis and immunosuppression in ducks, leading to substantial economic losses in the duck farming industry. While the avian orthoreovirus (ARV) σA protein is known to exhibit interferon (IFN) antagonistic activity, whether NDRV possesses a similar function and the underlying molecular mechanisms remain unclear. This study demonstrates that NDRV not only counteracts the antiviral clearance effect of type I IFN (IFN-I) but also markedly suppresses IFN-mediated signal transduction. Further investigations revealed that the NDRV σA protein specifically inhibits IFN signaling and its associated antiviral effects by blocking the nuclear translocation of STAT1/STAT2, thereby, facilitating innate immune escape. This discovery elucidates for the first time a novel mechanism by which the NDRV σA protein regulates the JAK-STAT signaling pathway. These findings provide a theoretical foundation for the development of antiviral strategies targeting immune regulation.

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新型鸭正呼肠孤病毒σA蛋白通过抑制STAT1/STAT2核易位抑制干扰素信号传导

新型鸭正呼肠孤病毒（NDRV）感染会引起鸭严重的脾坏死和免疫抑制，给养鸭业带来巨大的经济损失。虽然已知禽正呼肠孤病毒(ARV) σA蛋白具有干扰素（IFN）拮抗活性，但NDRV是否具有类似的功能及其潜在的分子机制尚不清楚。本研究表明，NDRV不仅可以抵消I型IFN （IFN-I）的抗病毒清除作用，还可以显著抑制IFN介导的信号转导。进一步研究发现，NDRV σA蛋白通过阻断STAT1/STAT2的核易位，特异性抑制IFN信号及其抗病毒作用，从而促进先天免疫逃逸。这一发现首次阐明了NDRV σA蛋白调控JAK-STAT信号通路的新机制。这些发现为开发靶向免疫调节的抗病毒策略提供了理论基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transboundary and Emerging Diseases 农林科学-传染病学

CiteScore

8.90

自引率

9.30%

发文量

350

审稿时长

1 months

期刊介绍： Transboundary and Emerging Diseases brings together in one place the latest research on infectious diseases considered to hold the greatest economic threat to animals and humans worldwide. The journal provides a venue for global research on their diagnosis, prevention and management, and for papers on public health, pathogenesis, epidemiology, statistical modeling, diagnostics, biosecurity issues, genomics, vaccine development and rapid communication of new outbreaks. Papers should include timely research approaches using state-of-the-art technologies. The editors encourage papers adopting a science-based approach on socio-economic and environmental factors influencing the management of the bio-security threat posed by these diseases, including risk analysis and disease spread modeling. Preference will be given to communications focusing on novel science-based approaches to controlling transboundary and emerging diseases. The following topics are generally considered out-of-scope, but decisions are made on a case-by-case basis (for example, studies on cryptic wildlife populations, and those on potential species extinctions): Pathogen discovery: a common pathogen newly recognised in a specific country, or a new pathogen or genetic sequence for which there is little context about — or insights regarding — its emergence or spread. Prevalence estimation surveys and risk factor studies based on survey (rather than longitudinal) methodology, except when such studies are unique. Surveys of knowledge, attitudes and practices are within scope. Diagnostic test development if not accompanied by robust sensitivity and specificity estimation from field studies. Studies focused only on laboratory methods in which relevance to disease emergence and spread is not obvious or can not be inferred (“pure research” type studies). Narrative literature reviews which do not generate new knowledge. Systematic and scoping reviews, and meta-analyses are within scope.