Grass Carp Reovirus Major Outer Capsid Protein VP4 Interacts with RNA Sensor RIG-I to Suppress Interferon Response

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2020-04, Vol.10 (4), p.560
• Main Authors: Su, Hang, Fan, Chengjian, Liao, Zhiwei, Yang, Chunrong, Clarke, Jihong Liu, Zhang, Yongan, Su, Jianguo
• Format: Article
• Language: English
• Subjects: Animals; Aquaculture; Capsid protein; Capsid Proteins - metabolism; Carp; Carps - metabolism; Carps - virology; Cell Line; Complementation; Double-stranded RNA; Drug resistance; Endoplasmic Reticulum - metabolism; Endosomes - metabolism; Epidemics; Fish; Food industry; Food safety; Food sources; Gene expression; Genomes; Grass carp; grass carp reovirus (GCRV); Health aspects; Host-virus relationships; host/pathogen protein interaction; immune evasion; Immunoglobulins; Immunoprecipitation; Infections; Interferon; Interferons - metabolism; Kidneys; Kinases; Lysosomes - metabolism; major outer capsid protein VP4; molecular function; MyD88 protein; Observations; Pathogens; Pattern recognition; Protein Transport; Proteins; Reoviridae - genetics; Reoviridae - physiology; Reoviruses; RIG-I-like receptor signaling pathway; RNA, Viral - metabolism; Signal transduction; Ubiquitination; Viral infections; Viral proteins; Viruses
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10040560

Diseases caused by viruses threaten the production industry and food safety of aquaculture which is a great animal protein source. Grass carp reovirus (GCRV) has caused tremendous loss, and the molecular function of viral proteins during infection needs further research, as for most aquatic viruses. In this study, interaction between GCRV major outer capsid protein VP4 and RIG-I, a critical viral RNA sensor, was screened out by GST pull-down, endogenous immunoprecipitation and subsequent LC-MS/MS, and then verified by co-IP and an advanced far-red fluorescence complementation system. VP4 was proved to bind to the CARD and RD domains of RIG-I and promoted K48-linked ubiquitination of RIG-I to degrade RIG-I. VP4 reduced mRNA and promoter activities of key genes of RLR pathway and sequential IFN production. As a consequence, antiviral effectors were suppressed and GCRV replication increased, resulting in intensified cytopathic effect. Furthermore, results of transcriptome sequencing of VP4 stably expressed CIK ( kidney) cells indicated that VP4 activated the MyD88-dependent TLR pathway. Knockdown of VP4 obtained opposite effects. These results collectively revealed that VP4 interacts with RIG-I to restrain interferon response and assist GCRV invasion. This study lays the foundation for anti-dsRNA virus molecular function research in teleost and provides a novel insight into the strategy of immune evasion for aquatic virus.