脑心肌炎病毒结构蛋白 VP3 与 MAVS 相互作用并促进其自噬降解，从而干扰 I 型干扰素信号通路。

Encephalomyocarditis Virus Structural Protein VP3 Interacts with MAVS and Promotes its Autophagic Degradation to Interfere with the Type I Interferon Signaling Pathway.

机构信息

College of Life Science and Engineering, Northwest Minzu University, 730030 Lanzhou, Gansu, China.

Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, 730030 Lanzhou, Gansu, China.

出版信息

Front Biosci (Landmark Ed). 2024 Jul 25;29(7):273. doi: 10.31083/j.fbl2907273.

DOI:10.31083/j.fbl2907273

PMID:39082353

Abstract

BACKGROUND

Understanding the mechanisms through which interferon (IFN) signaling is negatively regulated is crucial for preserving the equilibrium of innate immune reactions, as the innate immune system functions, such as the original barrier, combat threats to the host. Although the function of the encephalomyocarditis virus (EMCV) viral proteins in antagonizing innate immunity has been related to earlier studies, the precise mechanism underlying the role of viral protein 3 (VP3) in type I IFN has yet to be fully illuminated.

METHODS

VP3 expression and many other adaptor molecules belonging to type I IFN pathway expression levels were evaluated using Western blotting. The IFN and other antiviral genes, such as interferon-stimulated genes (ISGs) 15 and 56, were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). A 50% tissue culture infectious dose (TCID50) assay was utilized to explore the effect of VP3 on EMCV proliferation in human embryonic kidney (HEK293) cells. Co-immunoprecipitation (Co-IP) assays and confocal microscope analysis were used to investigate the underlying mechanisms mediated by VP3.

RESULTS

We discovered that the VP3 of EMCV acts as a suppressor of innate immune reactions. Increased levels of VP3 enhance viral reproduction through modulation of innate immune signaling pathways and suppression of antiviral responses. Additional information indicated that during viral infection, the VP3 of EMCV enhances autophagy and interacts specifically with mitochondrial antiviral signaling protein (MAVS), leading to its degradation in an autophagy pathway that relies on p62.

CONCLUSIONS

Our findings showed that EMCV developed a tactic to combat host antiviral defenses by using autophagy to break down a protein that controls the innate immune response following a viral infection of the host. Notably, VP3 plays an important role in this process. Overall, these discoveries may provide a novel therapeutic target for EMCV.

摘要

背景

理解干扰素（IFN）信号负调控的机制对于维持先天免疫反应的平衡至关重要，因为先天免疫系统的功能，如原始屏障，可抵御宿主面临的威胁。尽管脑炎心肌炎病毒（EMCV）病毒蛋白在拮抗先天免疫方面的功能已与早期研究相关，但病毒蛋白 3（VP3）在 I 型 IFN 中的作用的确切机制尚未完全阐明。

方法

使用 Western blot 评估 VP3 表达和属于 I 型 IFN 途径表达水平的许多其他衔接分子。通过实时定量聚合酶链反应（RT-qPCR）评估 IFN 和其他抗病毒基因，如干扰素刺激基因（ISGs）15 和 56。利用 50%组织培养感染剂量（TCID50）测定法研究 VP3 对 EMCV 在人胚肾（HEK293）细胞中增殖的影响。使用共免疫沉淀（Co-IP）测定法和共聚焦显微镜分析来研究由 VP3 介导的潜在机制。