Regulation of Retinoic Acid Inducible Gene-I (RIG-I) Activation by the Histone Deacetylase 6

Liu, Helene Minyi; Jiang, Fuguo; Loo, Yueh–Ming; Hsu, Shu Zhen; Hsiang, Tien Ying; Marcotrigiano, Joseph; Gale, Michael

doi:10.1016/j.ebiom.2016.06.015

Cited by 66 publications

(64 citation statements)

References 56 publications

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“…It is possible that a certain amount of YY1 molecules is required to bind to the -90 and -120 sites of IFN-β promoter, allowing the recruitment of virus-induced histone acetyltransferases (HATs) and the acetylation of lysine residues of histone H4 and H3 at the IFN-β promoter region, in order to activate IFN-β transcription [17, 18]. In addition to the interaction with HATs, YY1 was reported to interact with histone deacetylases [38], which play crucial roles in the regulation of RIG-I activation during antiviral immune response [39]. Therefore, the required levels of YY1 may facilitate the activation of TBK1 and IRF3 during viral infection.…”

Section: Discussionmentioning

confidence: 99%

Yin Yang 1 Dynamically Regulates Antiviral Innate Immune Responses During Viral Infection

Zan

Zhang²,

et al. 2017

Cell Physiol Biochem

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Background/Aims: Type I interferon (IFN-1) production and IFN-1 signaling play critical roles in the host antiviral innate immune responses. Although transcription factor Yin Yang 1 (YY1) has been reported to have a dual activator/repressor role during the regulation of interferon beta (IFN-β) promoter activity, the roles of YY1 in the regulation of upstream signaling pathways leading to IFN-1 induction and IFN-1 signaling during viral infection remain to be elucidated. Methods: The roles of YY1 in IFN-1 production and IFN-1 signaling were investigated using immunoblotting, real-time PCR, small interfering RNA (siRNA)-mediated YY1 knockdown, YY1 overexpression by transient transfection, and co-immunoprecipitation, using mouse cells. Results: YY1 was shown to interact with STAT1 in the absence of viral infection. Following viral infection, YY1 protein expression levels were decreased. YY1 knockdown led to a considerable downregulation of phosphorylated (p) TBK1 and pIRF3 expressions, while YY1 overexpression significantly upregulated pTBK1 and pIRF3 expression levels and promoted virus-induced IFN-β production. Additionally, YY1 knockdown led to a significant upregulation of pSTAT1, pSTAT2 and antiviral interferon-stimulated genes, and inhibited viral replication. Conclusion: We demonstrated here that YY1 interacts with STAT1 and dynamically regulates the induction of IFN-1 production and activation of IFN-1 signaling in different stages during viral infection.

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Section: Discussionmentioning

confidence: 99%

Yin Yang 1 Dynamically Regulates Antiviral Innate Immune Responses During Viral Infection

Zan

Zhang²,

et al. 2017

Cell Physiol Biochem

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“…RIG-I is a key cytosolic sensor that recognizes and binds to 5¢-triphosphate dsRNA of RNA viruses. In resting cells, the K858 and K909 residue of RIG-I are acetylated, which reduce its translocation to the intracellular membranes and its 5¢-triphosphate dsRNA binding ability [105,106]. Upon virus infection, HDAC6-mediated deacetylation of RIG-I is critical for viral RNA detection [105,106].…”

Section: Controlling Antiviral Immune Responsesmentioning

confidence: 99%

“…In resting cells, the K858 and K909 residue of RIG-I are acetylated, which reduce its translocation to the intracellular membranes and its 5¢-triphosphate dsRNA binding ability [105,106]. Upon virus infection, HDAC6-mediated deacetylation of RIG-I is critical for viral RNA detection [105,106]. HDAC6 transiently binds to RIG-I and removes the Lys 909 acetylation in the presence of viral RNAs, promoting RIG-I oligomerization and sensing of viral RNAs, leading to the activation of downstream signalling, Mitochondrial Antiviral Signaling Protein (MAVS)-IRF-3-NF-kB and finally the expression of IFN-b and a variety of antiviral and immunomodulatory genes (Fig.…”

Section: Controlling Antiviral Immune Responsesmentioning

confidence: 99%

“…3b). Consequently, like IRF-3 -/-mice, HDAC6 -/-mice are highly susceptible to RNA virus infection, highlighting the importance of HDAC6 in triggering innate antiviral immune signalling [104][105][106]. In the future, it will also be interesting to examine the role of HDAC6 in the antiviral immune response against DNA virus infection.…”

Section: Controlling Antiviral Immune Responsesmentioning

confidence: 99%

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Cellular defence or viral assist: the dilemma of HDAC6

Zheng

Jiang

et al. 2017

Journal of General Virology

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Histone deacetylase 6 (HDAC6) is a unique cytoplasmic deacetylase that regulates various important biological processes by preventing protein aggregation and deacetylating different non-histone substrates including tubulin, heat shock protein 90, cortactin, retinoic acid inducible gene I and b-catenin. Growing evidence has indicated a dual role for HDAC6 in viral infection and pathogenesis: HDAC6 may represent a host defence mechanism against viral infection by modulating microtubule acetylation, triggering antiviral immune response and stimulating protective autophagy, or it may be hijacked by the virus to enhance proinflammatory response. In this review, we will highlight current data illustrating the complexity and importance of HDAC6 in viral pathogenesis. We will summarize the structure and functional specificity of HDAC6, and its deacetylaseand ubiquitin-dependent activity in key cellular events in response to virus infection. We will also discuss how HDAC6 exerts its direct or indirect histone modification ability in viral lytic-latency switch.

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“…Retinoic acid inducible gene‐I (RIG‐I) is a caspase recruitment domain (CARD) containing protein that acts as an intracellular RNA receptor. When it detects the presence of cytoplasmic viral nucleic acids and other pathogens, it triggers innate immunity and signals the initiation of the immune response against RNA virus infection [Barrat et al, ; Liu et al, ]. The means by which mitochondria take charge of antiviral innate immune responses have not been fully characterized, and the multiple names given to some genes and their protein products involved in the signaling pathways can be confusing.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Treatment of Persistent Viral Infections

Moos¹,

Pinkert

Irwin

et al. 2016

Drug Development Research

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Preclinical Research Approximately 2,500 years ago, Hippocrates used the word herpes as a medical term to describe lesions that appeared to creep or crawl on the skin, advocating heat as a possible treatment. During the last 50 years, pharmaceutical research has made great strides, and therapeutic options have expanded to include small molecule antiviral agents, protease inhibitors, preventive vaccines for a handful of the papillomaviruses, and even cures for hepatitis C virus infections. However, effective treatments for persistent and recurrent viral infections, particularly the highly prevalent herpesviruses, continue to represent a significant unmet medical need, affecting the majority of the world's population. Exploring the population diversity of the human microbiome and the effects its compositional variances have on the immune system, health, and disease are the subjects of intense investigational research and study. Among the collection of viruses, bacteria, fungi, and single-cell eukaryotes that comprise the human microbiome, the virome has been grossly understudied relative to the influence it exerts on human pathophysiology, much as mitochondria have until recently failed to receive the attention they deserve, given their critical biomedical importance. Fortunately, cellular epigenetic machinery offers a wealth of druggable targets for therapeutic intervention in numerous disease indications, including those outlined above. With advances in synthetic biology, engineering our body's commensal microorganisms to seek out and destroy pathogenic species is clearly on the horizon. This is especially the case given recent breakthroughs in genetic manipulation with tools such as the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) gene-editing platforms. Tying these concepts together with our previous work on the microbiome and neurodegenerative and neuropsychiatric diseases, we suggest that, because mammalian cells respond to a viral infection by triggering a cascade of antiviral innate immune responses governed substantially by the cell's mitochondria, small molecule carnitinoids represent a new class of therapeutics with potential widespread utility against many infectious insults. Drug Dev Res 78 : 24-36, 2017. © 2016 Wiley Periodicals, Inc.

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Regulation of Retinoic Acid Inducible Gene-I (RIG-I) Activation by the Histone Deacetylase 6

Cited by 66 publications

References 56 publications

Yin Yang 1 Dynamically Regulates Antiviral Innate Immune Responses During Viral Infection

Yin Yang 1 Dynamically Regulates Antiviral Innate Immune Responses During Viral Infection

Cellular defence or viral assist: the dilemma of HDAC6

Epigenetic Treatment of Persistent Viral Infections

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