The crosstalk between viral RNA- and DNA-sensing mechanisms

Cai, Chunmei; Tang, Yan-Dong; Xu, Guocai; Zheng, Chunfu

doi:10.1007/s00018-021-04001-7

Cited by 36 publications

(32 citation statements)

References 76 publications

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“…204 Following the recognition of distinct dsRNA features, the N-terminal caspase activation and recruitment domains (CARDs) of RIG-I and MDA5 but not LGP2 can recruit and activate the downstream adaptor mitochondrial antiviral signaling (MAVS) protein, located at the outer mitochondrial membrane. 205,206 Subsequently, the activated MAVS protein recruits downstream proteins TBK1 and IKK-related kinases IKKε to phosphorylate and activate IRF3/7 via the TRAF3-TANK-TBK1 axis, as well as canonical IKKα/β/γ complex to promote degradation of the NF-κB inhibitor IκBα through the FADD-RIP1-IKK axis, leading to NF-κB activation, which ultimately accompanies some other transcription factor to stimulate the expression of IFN-I and proinflammatory cytokines. [207][208][209] Several studies have identified that RNF proteins emerged as key regulators of RLR-triggered antiviral response (Fig.…”

Section: Rlr Signaling Pathwaymentioning

confidence: 99%

The RING finger protein family in health and disease

Cai

Tang

Zhai³

et al. 2022

Sig Transduct Target Ther

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Ubiquitination is a highly conserved and fundamental posttranslational modification (PTM) in all eukaryotes regulating thousands of proteins. The RING (really interesting new gene) finger (RNF) protein, containing the RING domain, exerts E3 ubiquitin ligase that mediates the covalent attachment of ubiquitin (Ub) to target proteins. Multiple reviews have summarized the critical roles of the tripartite-motif (TRIM) protein family, a subgroup of RNF proteins, in various diseases, including cancer, inflammatory, infectious, and neuropsychiatric disorders. Except for TRIMs, since numerous studies over the past decades have delineated that other RNF proteins also exert widespread involvement in several diseases, their importance should not be underestimated. This review summarizes the potential contribution of dysregulated RNF proteins, except for TRIMs, to the pathogenesis of some diseases, including cancer, autoimmune diseases, and neurodegenerative disorder. Since viral infection is broadly involved in the induction and development of those diseases, this manuscript also highlights the regulatory roles of RNF proteins, excluding TRIMs, in the antiviral immune responses. In addition, we further discuss the potential intervention strategies targeting other RNF proteins for the prevention and therapeutics of those human diseases.

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Section: Rlr Signaling Pathwaymentioning

confidence: 99%

The RING finger protein family in health and disease

Cai

Tang

Zhai³

et al. 2022

Sig Transduct Target Ther

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“…Several investigations have indicated that patients with severe SLE express high levels of ISGs in peripheral blood mononuclear cells (PBMCs) [ 9 , 10 ]. In addition, several studies have revealed that activation via nucleic acid–sensor pathways induces IFNs-I production [ 11 , 12 , 13 ]. Interestingly, the stimulator of interferon genes (STING) is a cytoplasmic adaptor protein residing in the ER membrane that signals transduction to increase IFNs-I and pro-inflammatory cytokine production [ 14 , 15 ] through cyclic GMP–AMP synthase (cGAS)-mediated cGAMP [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects of Red Rice Bran Extract Ameliorate Type I Interferon Production via STING Pathway

Onsa-ard

Thongboontho

Munkong

et al. 2022

Foods

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Type I interferons (IFNs-I) are inflammatory cytokines that play an essential role in the pathogenesis of inflammation and autoimmune diseases. Signaling through nucleic acid sensors causes the production of IFNs-I. A stimulator of interferon genes (STING) is a DNA sensor that signals transduction, leading to the production of IFNs-I after their activation. This study aims to determine the anti-inflammatory effects of red rice bran extract (RRBE) on macrophages through the activation of STING signaling. RAW264.7 macrophage cells were stimulated with STING agonist (DMXAA) with and without RRBE. Cells and supernatant were collected. The level of mRNA expression was determined by qPCR, and inflammatory cytokine production was investigated by ELISA. The results indicate that RRBE significantly lowers the transcription of Sting and interferon-stimulated genes (ISGs). Moreover, RRBE suppresses the phosphorylation of STING, leading to a decrease in the expression of Irf3, a transcription factor that initiates IFN-I signaling. Our results provide evidence that red rice bran extract may be a protective compound for inflammatory diseases by targeting STING signaling.

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“…Innate immune cells, including macrophages, dendritic cells, neutrophils, innate lymphoid cells among other cell types, constitute the front line of the defense against pathogen infections. These cells express germline-encoded pattern recognition receptors (PRRs) that recognize evolutionary conserved microbial structures, named pathogen-associated molecular patterns (PAMPs), as well as endogenous molecules released from damaged cells, known as damage associated molecular patterns (DAMPs) (65,66). The knowledge of novel PPRs and pathways is under constant development, due to review scope limitations, the PRR families discussed here are the Toll-like receptors (TLRs), retinoic acid-inducible gene I-like receptors (RLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and the cytosolic dsDNA sensors (CDS).…”

Section: Innate Immune Modulation As a Putative Host Directed Antivir...mentioning

confidence: 99%

“…The ligands and signaling mechanisms differ in the different PRRs families. However, they do share common features: upon a PAMPs or DAMPs recognition, signaling cascades will generally lead to the production of type I interferon (IFN-I), the induction of a huge amount of interferon stimulated genes (ISGs) and the release of proinflammatory cytokines and chemokines, which in an autocrine and paracrine manner, will promote an antiviral state, the pathogen clearance as well as the priming of the adaptive immunity (66,68). Interestingly, the PRRs sensing pathways have been shown to be interconnected.…”

Section: Innate Immune Modulation As a Putative Host Directed Antivir...mentioning

confidence: 99%

Viral-Host Dependency Factors as Therapeutic Targets to Overcome Antiviral Drug-Resistance: A Focus on Innate Immune Modulation

Badía

García-Vidal²,

Ballana³

2022

Front. Virol.

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The development of antiviral drugs, has provided enormous achievements in our recent history in the fight against viral infections. To date, most of the approved antiviral drugs target virus-encoded proteins to achieve direct antiviral activity. Nonetheless, the inherent idiosyncrasy of viral mutations during their replication cycle, enable many viruses to adapt to the new barriers, becoming resistant to therapies, therefore, representing an ever-present menace and prompting the scientific community towards the development of novel therapeutic strategies. Taking advantage of the increasing knowledge of virus-host cell interactions, the targeting of cellular factors or pathways essential for virus survival turns into an alternative strategy to intervene in almost every step of viral replication cycle. Since host factors are evolutionary conserved, viral evasion to host-directed therapies (HDT) would impose a higher genetic barrier to the emergence of resistant strains. Thus, targeting host factors has long been considered an alternative strategy to overcome viral resistance. Nevertheless, targeting host factors or pathways potentially hints undesired off targets effects, and therefore, a critical risk-benefit evaluation is required. The present review discusses the current state-of-the-art on the identification of viral host dependency factors (HDF) and the workflow required for the development of HDT as antivirals. Then, we focus on the feasibility of using a specific class of host factors, those involved in innate immune modulation, as broad-spectrum antiviral therapeutic strategies. Finally, a brief summary of major roadblocks derived from targeting host cellular proteins and putative future strategies to overcome its major limitations is proposed.

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The crosstalk between viral RNA- and DNA-sensing mechanisms

Cited by 36 publications

References 76 publications

The RING finger protein family in health and disease

The RING finger protein family in health and disease

Anti-Inflammatory Effects of Red Rice Bran Extract Ameliorate Type I Interferon Production via STING Pathway

Viral-Host Dependency Factors as Therapeutic Targets to Overcome Antiviral Drug-Resistance: A Focus on Innate Immune Modulation

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