Crosstalk between Autophagy and RLR Signaling

Abstract

Autophagy plays a homeostatic role in regulating cellular metabolism by degrading unwanted intracellular materials and acts as a host defense mechanism by eliminating infecting pathogens, such as viruses. Upon viral infection, host cells often activate retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling to induce the transcription of type I interferons, thus establishing the first line of the innate antiviral response. In recent years, numerous studies have shown that virus-mediated autophagy activation may benefit viral replication through different actions on host cellular processes, including the modulation of RLR-mediated innate immunity. Here, an overview of the functional molecules and regulatory mechanism of the RLR antiviral immune response as well as autophagy is presented. Moreover, a summary of the current knowledge on the biological role of autophagy in regulating RLR antiviral signaling is provided. The molecular mechanisms underlying the crosstalk between autophagy and RLR innate immunity are also discussed.

Respiratory RNA viruses: Molecular mechanisms of viral replication and pathogenicity

“…The second pathway recruits the tumor necrosis factor receptor-associated factor 6 (TRAF6) and nuclear factor-κb (NF-κB) inhibitor IKK complex to phosphorylate the inhibitor of κB (IκB), after which phosphorylated IκB is recognized by the β-Transducin repeats-containing protein (β-TrCP), the substrate recognition subunit of the SCF (SKP1, CUL1, and F-box protein)-type E3 ubiquitin ligase complex and is then cleaved by the proteasome to release NF-κB. Finally, activated IRF3 and NF-κB are transported to the nucleus to promote the expression of IFNs and proinflammatory cytokines (Hou, 2021;Ke, 2023). After secretion, IFN binds to specific receptors on the cell surface to activate the intracellular Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, which ultimately leads to the expression of hundreds of interferon-stimulated genes (ISGs), activating host immune responses and inflammation (Figure 2 right) (Ke, 2023).…”

“…Finally, activated IRF3 and NF-κB are transported to the nucleus to promote the expression of IFNs and proinflammatory cytokines (Hou, 2021;Ke, 2023). After secretion, IFN binds to specific receptors on the cell surface to activate the intracellular Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, which ultimately leads to the expression of hundreds of interferon-stimulated genes (ISGs), activating host immune responses and inflammation (Figure 2 right) (Ke, 2023).…”

Molecular biology of canine parainfluenza virus V protein and its potential applications in tumor immunotherapy

“…The second pathway recruits the tumor necrosis factor receptor-associated factor 6 (TRAF6) and nuclear factor-κb (NF-κB) inhibitor IKK complex to phosphorylate the inhibitor of κB (IκB), after which phosphorylated IκB is recognized by the β-Transducin repeats-containing protein (β-TrCP), the substrate recognition subunit of the SCF (SKP1, CUL1, and F-box protein)-type E3 ubiquitin ligase complex and is then cleaved by the proteasome to release NF-κB. Finally, activated IRF3 and NF-κB are transported to the nucleus to promote the expression of IFNs and proinflammatory cytokines ( Hou, 2021 ; Ke, 2023 ). After secretion, IFN binds to specific receptors on the cell surface to activate the intracellular Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, which ultimately leads to the expression of hundreds of interferon-stimulated genes (ISGs), activating host immune responses and inflammation ( Figure 2 right) ( Ke, 2023 ).…”

“…Finally, activated IRF3 and NF-κB are transported to the nucleus to promote the expression of IFNs and proinflammatory cytokines ( Hou, 2021 ; Ke, 2023 ). After secretion, IFN binds to specific receptors on the cell surface to activate the intracellular Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, which ultimately leads to the expression of hundreds of interferon-stimulated genes (ISGs), activating host immune responses and inflammation ( Figure 2 right) ( Ke, 2023 ).…”

“…Recent studies have shown that virus-mediated autophagy activation negatively regulates the host innate immune response mediated by PRRs such as RIG-1 and MDA5, thereby promoting virus replication ( Wu et al, 2021 ; Ke, 2023 ). In addition, in a study of Sendai virus (SeV), autophagy-related receptor coiled-coil domain containing protein 50 (CCDC50) inhibited the recruitment of downstream MAVS proteins by RIG-1/MDA5 and targeted them for autophagic degradation.…”