Orange-spotted grouper nervous necrosis virus-encoded protein A induces interferon expression via RIG-I/MDA5-MAVS-TBK1-IRF3 signaling in fish cells

Author:

Huang Siyou1ORCID,Huang Yi1,Su Taowen1,Huang Runqing2,Su Lianpan1,Wu Yujia1,Weng Shaoping1,He Jianguo1ORCID,Xie Junfeng1ORCID

Affiliation:

1. State Key Laboratory of Biocontrol, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), China-ASEAN Belt and Road Joint Laboratory on Mariculture Technology, Guangdong Provincial Key Laboratory of Aquatic Economic Animals, Sun Yat-sen University , Guangzhou, China

2. School of Life Science, Huizhou University , Huizhou, China

Abstract

ABSTRACT Nervous necrosis virus (NNV), a highly contagious fish virus, has caused huge economic losses to the global aquaculture industry. A previous study showed that protein A (ProA) encoded by orange-spotted grouper NNV triggers type I interferon (IFN) production in fish cells, but the activation and modulation of correlative signal pathways remain unclear. Here, we proved that ProA induces fish cell-specific IFN promoter activation in a dose-dependent manner. In channel catfish ovary (CCO, an NNV-permissive cell), ProA evoked expression and secretion of functional IFN with anti-DNA virus activity, suggesting a good model for IFN signaling research. A contrastive study of signaling in CCO and fathead minnow (FHM, an NNV-nonpermissive cell) using RNAi knockdown or dominant negative mutant overexpression verified that ProA-mediated IFN activation went through retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) pathway (RIG-I/MDA5-MAVS-TRAF3-TBK1-IRF3) while NOD1-RIPK2-NFκB and TLR3-TRIF branches were unnecessary. As RNA receptors upregulated by ProA in FHM, RIG-I and MDA5 promoted ProA-mediated IFN activation to form a positive feedback loop, while LGP2, NOD1, and PKR inhibited this activation as negative modulators. In ProA-expressed, NNV-infected CCO, the transcription of RIG-I, MDA5, MAVS, TBK1, IRF3, and IFN was downregulated, but the expression of LGP2, TRAF3, and NOD1 remained unchanged, suggesting unknown IFN suppression mechanism by NNV infection. IFN inhibition by overexpressing mutated RIG-I greatly enhanced NNV replication in FHM, implying that RIG-I might be the main target for both ProA-mediated activation and NNV infection-induced inhibition. This study provides overviews and foundations for understanding the interaction between betanodavirus-encoded protein and fish innate immune signaling. IMPORTANCE As a major pathogen, nervous necrosis virus (NNV) infects more than 120 fish species worldwide and is virulent to larvae and juvenile fish, hampering the development of the fish fry industry. Understanding virus-host interaction and underlying mechanisms is an important but largely unknown issue in fish virus studies. Here, using channel catfish ovary and fathead minnow cells as models for the study of innate immunity signaling, we found that NNV-encoded ProA activated interferon signaling via the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) pathway which was still suppressed by the infection of wild-type NNV. This finding has important implications for the comprehension of NNV protein function and the immune response from different cells. First, RIG-I is the key node for anti-NNV innate immunity. Second, the response intensity of RLR signaling determines the degree of NNV proliferation. This study expands our knowledge regarding the overview of signal pathways affected by NNV-encoded protein and also highlights potential directions for the control of aquatic viruses.

Funder

China Agricultural Research System

MOST | National Natural Science Foundation of China

GDSTC | Natural Science Foundation of Guangdong Province

Key Research and Development Program of Guangdong Province

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3