Abstract
The RIG-I-like receptors (RLRs) signaling pathway is essential for inducing type I interferon (IFN) responses to viral infections. Meanwhile, it is also tightly regulated to prevent uncontrolled immune responses. Numerous studies have shown that microRNAs (miRNAs) are essential for the regulation of immune processes, however, the detailed molecular mechanism of miRNA regulating the RLRs signaling pathway remains to be elucidated. Here, our results showed that miR-202-5p was induced by red spotted grouper nervous necrosis virus (RGNNV) infection in zebrafish. Overexpression of miR-202-5p led to reduced expression of IFN 1 and its downstream antiviral genes, thus facilitating viral replication in vitro. In comparison, significantly enhanced levels of IFN 1 and antiviral genes and significantly low viral burden were observed in the miR-202-5p-/- zebrafish compared to wild type zebrafish. Subsequently, zebrafish tripartite motif-containing protein 25 (zbTRIM25) was identified as a target of miR-202-5p in both zebrafish and humans. Ectopic expression of miR-202-5p suppressed zbTRIM25-mediated RLRs signaling pathway. Furthermore, we showed that miR-202-5p inhibited zbTRIM25-mediated zbRIG-I ubiquitination and activation of IFN production. In conclusion, we demonstrate that RGNNV-inducible miR-202-5p acts as a negative regulator of zbRIG-I-triggered antiviral innate response by targeting zbTRIM25. Our study reveals a novel mechanism for the evasion of the innate immune response controlled by RGNNV.
Highlights
The innate immune system is the first defense line that recognizes pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) against microbial pathogen invasion [1]
Our findings reveal a novel mechanism of red spotted grouper nervous necrosis virus (RGNNV) to inhibit Retinoic acid inducible gene-I (RIG-I)-like receptors (RLRs) signaling pathway by miR-202-5p and will help to develop new treatments for viral nervous necrosis disease
To investigate the roles of host miRNAs during RGNNV infection, a miRNA profile was obtained from the mock and RGNNV infected ZBE3 cells to analyze the relationship between miRNAs and RGNNV
Summary
The innate immune system is the first defense line that recognizes pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) against microbial pathogen invasion [1]. Retinoic acid inducible gene-I (RIG-I)-like receptors (RLRs), comprised of RIG-I, melanoma differentiation–associated gene (MDA) 5, and laboratory of genetics and physiology (LGP) 2, recognize non-self-signatures of viral RNAs in the cytosol of cells and activate their downstream signal transduction to trigger host interferon (IFN) responses and eliminate invading viruses by induction of a wide range of IFN-stimulated genes (ISGs) [2]. Hosts and viruses have developed a variety of mechanisms to modulate the RLRs signaling pathway to avoid excessive IFN production and antagonize such innate antiviral responses via targeting multiple steps in the RLRs signaling pathway, respectively. Viruses 2020, 12, 261 β production by targeting RIG-I and MDA5 [3]. Ring finger protein (RNF) 122 targeted RIG-I for proteasomal degradation to inhibit RLRs-mediated IFN production [4]. Zebrafish RIG-I plays an essential role in group
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
