Transcriptome Analysis of Retinoic Acid-Inducible Gene I Overexpression Reveals the Potential Genes for Autophagy-Related Negative Regulation

Abstract

Retinoic acid-inducible gene I (RIG-I) serves as an essential viral RNA sensor for innate immune. The activation of the RIG-I-like receptors (RLRs) pathway triggers many regulations for the outcome of type I interferon, including ubiquitination, dephosphorylation, ISGylation, and autophagy. However, the autophagy-related regulation of RIG-I is still not fully understood. To investigate the potentially unknown genes related to autophagy-related regulation of RIG-I, we firstly confirm the induction of autophagy derived by overexpression of RIG-I. Furthermore, the autophagy inducer and inhibitor drugs were used in different assays. The results showed autophagy could control the activation of RLRs pathway and expression of exogenous RIG-I. In addition, we carried out the transcriptome analysis of overexpression of RIG-I in vitro. Differentially expressed genes (DEGs) in GO and KEGG signaling pathways enrichment provided a newly complex network. Finally, the validation of qPCR indicated that the DEGs PTPN22, PRKN, OTUD7B, and SIRT2 were correlated to the negative regulation of excessive expression of RIG-I. Taken together, our study contributed new insights into a more comprehensive understanding of the regulation of excessive expression of RIG-I. It provided the potential candidate genes for autophagy-related negative regulation for further investigation.

Feline Calicivirus P39 Inhibits Innate Immune Responses by Autophagic Degradation of Retinoic Acid Inducible Gene I

“…Our lab and a recent study have reported that the innate immune-associated molecules, RIG-I, could be degraded by autophagy [ 20 , 21 ]. Additionally, RIG-I is an important sensor for RNA viruses to trigger the interferon response.…”

“…Our lab has proved that feline RIG-I plays an essential role in the antiviral effect of FCV infection (not shown in this study). Moreover, our previous study indicated that autophagy could negatively regulate RIG-I [ 20 ]. In this study, we found that FCV infection triggered autophagy.…”

“…RIG-I is responsible for recognizing non-self RNA in the cytoplasm, such as viral RNA, which leads to the translocation of IRF-3 and NF-κB to induce the expression of type 1 interferon (IFN) and inflammatory cytokines, thereby mediating host antiviral immunity [ 17 , 18 ]. Additionally, RIG-I-mediated signaling can induce autophagy through the MAVS-TRAF6-Beclin1 signaling axis [ 19 ], and autophagy has been shown to regulate the activation of the RLRs pathway and expression of exogenous RIG-I [ 20 ]. Despite the progress made in understanding the pathogenesis and immune evasion strategies of FCV, the mechanisms of FCV replication and the host innate immune response remain largely unknown.…”

The ZIKV NS5 Protein Aberrantly Alters the Tubulin Cytoskeleton, Induces the Accumulation of Autophagic p62 and Affects IFN Production: HDAC6 Has Emerged as an Anti-NS5/ZIKV Factor

“…We observed that the ZIKV NS5 protein inhibited RNA-mediated RIG-I IFN production in HEK-Lucia™ RIG-I cells (Figure 5a, compared with cells not expressing NS5), a model for measuring IFN production in a 5' triphosphate hairpin RNA (3p-hpRNA) RIG-I agonist-dependent manner [159][160][161][162]. In the presence of 3-MA, NS5 completely abrogated the IFN response mediated by the RIG-I agonist 3p-hpRNA (Figure 5a).…”

The ZIKV NS5 Protein Aberrantly Alters the Tubulin Cytoskeleton, Induces the Accumulation of Autophagic p62 and Affects IFN Production: HDAC6 Has Emerged as an Anti-NS5/ZIKV Factor

“…We observed that the ZIKV NS5 protein inhibited RNA-mediated RIG-I IFN production in HEK-Lucia™ RIG-I cells (Figure 5a, compared with cells not expressing NS5), a model for measuring IFN production in a 5 ′ triphosphate hairpin RNA (3p-hpRNA) RIG-I agonist-dependent manner [159][160][161][162]. In the presence of 3-MA, NS5 strongly diminished the IFN response mediated by the RIG-I agonist 3p-hpRNA (Figure 5a).…”