Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling.
Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease. Retinoic acid-inducible gene-I (RIG-I) serves as an innate immune sensor and triggers antiviral responses upon recognizing viral infections including RSV. Since tripartite motif-containing protein 25 (TRIM25)-mediated K63-polyubiquitination is crucial for RIG-I activation, several viruses target initial RIG-I activation through ... ubiquitination. RSV NS1 and NS2 have been shown to interfere with RIG-I-mediated antiviral signaling. In this study, we explored the possibility that NS1 suppresses RIG-I-mediated antiviral signaling by targeting TRIM25. Ubiquitination of ectopically expressed RIG-I-2Cards domain was decreased by RSV infection, indicating that RSV possesses ability to inhibit TRIM25-mediated RIG-I ubiquitination. Similarly, ectopic expression of NS1 sufficiently suppressed TRIM25-mediated RIG-I ubiquitination. Furthermore, interaction between NS1 and TRIM25 was detected by a co-immunoprecipitation assay. Further biochemical assays showed that the SPRY domain of TRIM25, which is responsible for interaction with RIG-I, interacted sufficiently with NS1. Suppression of RIG-I ubiquitination by NS1 resulted in decreased interaction between RIG-I and its downstream molecule, MAVS. The suppressive effect of NS1 on RIG-I signaling could be abrogated by overexpression of TRIM25. Collectively, this study suggests that RSV NS1 interacts with TRIM25 and interferes with RIG-I ubiquitination to suppress type-I interferon signaling.
Mesh Terms:
A549 Cells, Cell Line, DEAD Box Protein 58, HEK293 Cells, Humans, Immunity, Innate, Polymerase Chain Reaction, Protein Binding, Respiratory Syncytial Virus, Human, Signal Transduction, Transcription Factors, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Ubiquitination, Viral Nonstructural Proteins
A549 Cells, Cell Line, DEAD Box Protein 58, HEK293 Cells, Humans, Immunity, Innate, Polymerase Chain Reaction, Protein Binding, Respiratory Syncytial Virus, Human, Signal Transduction, Transcription Factors, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, Ubiquitination, Viral Nonstructural Proteins
Viruses
Date: Dec. 14, 2017
PubMed ID: 30558248
View in: Pubmed Google Scholar
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