Lu Xiaobing, Yi Meisheng, Hu Zhe, Yang Taoran, Zhang Wanwan, Marsh E Neil G, Jia Kuntong
State Key Laboratory of Biocontrol, Southern Marine Sciences and Engineering Guangdong Laboratory (Zhuhai), School of Marine Sciences, Sun Yat-sen University, Guangzhou, Guangdong, 519082, China.
Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, Guangdong, 519082, China.
bioRxiv. 2024 Jan 10:2024.01.09.574905. doi: 10.1101/2024.01.09.574905.
Viperin is an antiviral protein that exhibits a remarkably broad spectrum of antiviral activity. Viperin-like proteins are found all kingdoms of life, suggesting it is an ancient component of the innate immune system. However, viruses have developed strategies to counteract viperin's effects. Here, we describe a feedback loop between viperin and viral hemorrhagic septicemia virus (VHSV), a common fish pathogen. We show that viperin (viperin) is induced by both IFN-independent and IFN-dependent pathways, with the C-terminal domain of viperin being important for its anti-VHSV activity. viperin exerts an antiviral effect by binding both the nucleoprotein (N) and phosphoprotein (P) of VHSV and induces their degradation through the autophagy pathway, which is an evolutionarily conserved antiviral mechanism. However, counteracting viperin's activity, N protein targets and degrades transcription factors that up-regulate viperin expression, interferon regulatory factor (IRF) 1 and IRF9, through ubiquitin-proteasome pathway. Together, our results reveal a previously unknown feedback loop between viperin and virus, providing potential therapeutic targets for VHSV prevention.
Viral hemorrhagic septicaemia (VHS) is a contagious disease caused by the viral hemorrhagic septicaemia virus (VHSV), which poses a threat to over 80 species of marine and freshwater fish. Currently, there are no effective treatments available for this disease. Understanding the mechanisms of VHSV-host interaction is crucial for preventing viral infections. Here, we found that, as an ancient antiviral protein, viperin degrades the N and P proteins of VHSV through the autophagy pathway. Additionally, the N protein also impacts the biological functions of IRF1 and IRF9 through the ubiquitin-proteasome pathway, leading to the suppression of viperin expression. Therefore, the N protein may serve as a potential virulence factor for the development of VHSV vaccines and screening of antiviral drugs. Our research will serve as a valuable reference for the development of strategies to prevent VHSV infections.
蝰蛇素是一种抗病毒蛋白，具有非常广泛的抗病毒活性。在所有生物界中都发现了类似蝰蛇素的蛋白，这表明它是先天免疫系统的一个古老组成部分。然而，病毒已经进化出对抗蝰蛇素作用的策略。在此，我们描述了蝰蛇素与病毒性出血性败血症病毒（VHSV，一种常见的鱼类病原体）之间的反馈回路。我们发现蝰蛇素可通过不依赖干扰素和依赖干扰素的途径被诱导产生，蝰蛇素的C末端结构域对其抗VHSV活性很重要。蝰蛇素通过结合VHSV的核蛋白（N）和磷蛋白（P）发挥抗病毒作用，并通过自噬途径诱导它们降解，这是一种进化上保守的抗病毒机制。然而，作为对蝰蛇素活性的对抗，N蛋白通过泛素 - 蛋白酶体途径靶向并降解上调蝰蛇素表达的转录因子，即干扰素调节因子（IRF）1和IRF9。总之，我们的结果揭示了蝰蛇素与病毒之间以前未知的反馈回路，为预防VHSV提供了潜在的治疗靶点。
病毒性出血性败血症（VHS）是由病毒性出血性败血症病毒（VHSV）引起的一种传染病，对80多种海洋和淡水鱼类构成威胁。目前，这种疾病没有有效的治疗方法。了解VHSV与宿主相互作用的机制对于预防病毒感染至关重要。在此，我们发现，作为一种古老的抗病毒蛋白，蝰蛇素通过自噬途径降解VHSV的N和P蛋白。此外，N蛋白还通过泛素 - 蛋白酶体途径影响IRF1和IRF9的生物学功能，导致蝰蛇素表达受到抑制。因此，N蛋白可能是开发VHSV疫苗和筛选抗病毒药物的潜在毒力因子。我们的研究将为制定预防VHSV感染的策略提供有价值的参考。
