Optineurin inhibits IBDV replication via interacting with VP1

IF 2.4 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology Pub Date : 2024-09-23 DOI:10.1016/j.vetmic.2024.110261

Zhixuan Xiong , Qinghua Zeng , Ying Hu , Chongde Lai , Huansheng Wu

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引用次数: 0

Abstract

Avibirnavirus, specifically Infectious Bursal Disease Virus (IBDV), is a highly contagious pathogen that causes significant economic losses in the poultry industry. The polymerase protein VP1 of IBDV is critical to the viral life cycle, facilitating the synthesis of viral mRNA and the genome. Previous studies have suggested that various host factors influence the regulation of IBDV polymerase activity. In this study, we identified that IBDV infection induces the expression of optineurin (OPTN), a mitophagy receptor and a protein associated with amyotrophic lateral sclerosis (ALS), as well as a negative regulator of interferon I production. The induced expression of OPTN acts as a suppressor of IBDV replication, a function dependent on its ubiquitin-binding domain (UBAN). Furthermore, we demonstrated that OPTN exerts its antiviral effects through direct interactions with VP1 and VP3, which inhibit the polymerase activity of VP1 by preventing K63-linked ubiquitination of VP1. To our knowledge, this study is the first to report that OPTN, upregulated during IBDV infection, functions as a novel antiviral host factor that limits the virus's replicative capacity, offering a potential target for anti-IBDV therapeutic strategies.

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Optineurin 通过与 VP1 相互作用抑制 IBDV 复制

阿维巴尼病毒，特别是传染性法氏囊病病毒（IBDV），是一种传染性极强的病原体，给家禽业造成了巨大的经济损失。IBDV 的聚合酶蛋白 VP1 对病毒的生命周期至关重要，可促进病毒 mRNA 和基因组的合成。以前的研究表明，各种宿主因素会影响 IBDV 聚合酶活性的调节。在这项研究中，我们发现 IBDV 感染会诱导 optineurin（OPTN）的表达，OPTN 是一种有丝分裂受体，是一种与肌萎缩性脊髓侧索硬化症（ALS）相关的蛋白质，也是干扰素 I 生成的负调控因子。OPTN 的诱导表达可抑制 IBDV 复制，这一功能依赖于其泛素结合结构域（UBAN）。此外，我们还证明了 OPTN 是通过与 VP1 和 VP3 直接相互作用来发挥其抗病毒作用的，后者通过阻止 VP1 的 K63 链接泛素化来抑制 VP1 的聚合酶活性。据我们所知，本研究首次报道了在 IBDV 感染过程中上调的 OPTN 作为一种新型抗病毒宿主因子限制了病毒的复制能力，为抗 IBDV 治疗策略提供了一个潜在靶点。

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

Veterinary microbiology 农林科学-兽医学

CiteScore

5.90

自引率

6.10%

发文量

221

审稿时长

52 days

期刊介绍： Veterinary Microbiology is concerned with microbial (bacterial, fungal, viral) diseases of domesticated vertebrate animals (livestock, companion animals, fur-bearing animals, game, poultry, fish) that supply food, other useful products or companionship. In addition, Microbial diseases of wild animals living in captivity, or as members of the feral fauna will also be considered if the infections are of interest because of their interrelation with humans (zoonoses) and/or domestic animals. Studies of antimicrobial resistance are also included, provided that the results represent a substantial advance in knowledge. Authors are strongly encouraged to read - prior to submission - the Editorials (''Scope or cope'' and ''Scope or cope II'') published previously in the journal. The Editors reserve the right to suggest submission to another journal for those papers which they feel would be more appropriate for consideration by that journal. Original research papers of high quality and novelty on aspects of control, host response, molecular biology, pathogenesis, prevention, and treatment of microbial diseases of animals are published. Papers dealing primarily with immunology, epidemiology, molecular biology and antiviral or microbial agents will only be considered if they demonstrate a clear impact on a disease. Papers focusing solely on diagnostic techniques (such as another PCR protocol or ELISA) will not be published - focus should be on a microorganism and not on a particular technique. Papers only reporting microbial sequences, transcriptomics data, or proteomics data will not be considered unless the results represent a substantial advance in knowledge. Drug trial papers will be considered if they have general application or significance. Papers on the identification of microorganisms will also be considered, but detailed taxonomic studies do not fall within the scope of the journal. Case reports will not be published, unless they have general application or contain novel aspects. Papers of geographically limited interest, which repeat what had been established elsewhere will not be considered. The readership of the journal is global.