Apoptosis, Toll-like, RIG-I-like and NOD-like Receptors Are Pathways Jointly Induced by Diverse Respiratory Bacterial and Viral Pathogens

Martı́nez, Isidoro; Oliveros, Juan Carlos; Cuesta, Isabel; Barrera, Jorge de la; Ausina, Vicente; Casals, Cristina; Lorenzo, Alba de; Garcı́a, Ernesto; García-Fojeda, Belén; Garmendía, Junkal; González-Nicolau, Mar; Lacoma, Alícia; Menéndez, Margarita; Moranta, David; Nieto, Amelia; Ortı́n, Juan; Pérez-González, Alicia; Prat, Cristina; Ramos‐Sevillano, Elisa; Regueiro, Verónica; Rodríguez-Frandsen, Ariel; Solı́s, Dolores; Yuste, José; Bengoechea, José A.; Melero, José A.

doi:10.3389/fmicb.2017.00276

Cited by 24 publications

(19 citation statements)

References 93 publications

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“…Infection with PR8 increased the recruitment of RIG-I to the mitochondria as compared to uninfected control cells (MOCK). This association was higher in cells infected with delNS1 than in cells infected with the PR8 virus, in agreement with the increased antiviral response observed in delNS1 infected cells [39,40]. The recruitment of RIG-I to mitochondrial fractions was not modified by Dot1L inhibition in delNS1 infection.…”

Section: Ns1 Protein Modulates the Dot1l Control Of Rig-i-mavs Associsupporting

confidence: 83%

“…The RNA analysis of genes involved in the interferon signaling pathway indicated that influenza virus infection stimulates TRIM25 expression, which in turn markedly decreases when infected human alveolar epithelial cells are treated with a Dot1L inhibitor (Table 1, Figure 6). Characterization of the immune response induced by different pathogens in murine alveolar macrophages infected at high MOI [40], showed a higher induction of TRIM25 expression in delNS1 infected cells compared with PR8 infection (data not shown). TRIM25-mediated ubiquitination stimulates RIG-I tetramerization, allowing RIG-I-MAVS interaction, which triggers the induction of the innate immune response [45][46][47].…”

Section: Discussionmentioning

confidence: 97%

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Interferon-β Stimulation Elicited by the Influenza Virus Is Regulated by the Histone Methylase Dot1L through the RIG-I-TRIM25 Signaling Axis

Marcos-Villar

Zamarreño

Garaigorta

et al. 2020

Cells

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Influenza virus infection increases the methylation of lysine 79 of histone 3 catalyzed by the Dot1L enzyme. The role of Dot1L against infections was highlighted by an increase of influenza A and vesicular stomatitis virus replication in Dot1L-inhibited cells mediated by a decreased antiviral response. Interferon-beta (IFN-β) reporter assays indicate that Dot1L is involved in the control of retinoic acid-inducible gene-I protein (RIG-I) signaling. Accordingly, Dot1L inhibition decreases the IFN-β promoter stimulation and RIG-I-mitochondria-associated viral sensor (RIG-I-MAVS) association upon viral infection. Replication of an influenza A virus lacking NS1 (delNS1), incapable of counteracting the antiviral response, is not affected by Dot1L inhibition. Consequently, RIG-I-MAVS association and nuclear factor-κB (NF-κB) nuclear translocation, are not affected by the Dot1L inhibition in delNS1 infected cells. Restoration of NS1 expression in trans also reinstated Dot1L as a regulator of the RIG-I-dependent signaling in delNS1 infections. Interferon-inducible E3 ligase tripartite motif-containing protein 25 (TRIM25) expression increases in influenza virus infected cells, but Dot1L inhibition reduces both the TRIM25 expression and TRIM25 protein levels. TRIM25 overexpression reverses the defective innate response mediated by Dot1L inhibition elicited upon virus infection or by overexpression of RIG-I signaling intermediates. Thus, TRIM25 is a control point of the RIG-I recognition pathway controlled by Dot1L and may have a general role in RNA viruses recognized by the RIG-I sensor.Cells 2020, 9, 732 2 of 20 H1N1 virus-infected cells, we observed unaltered DNA methylation and a general decrease in histone acetylation, which correlates with the cell host transcriptional inactivation that takes place during infection.Unexpectedly, we observed an increase in the methylation of lysine 79 of histone 3 (H3K79) in the infected cells [5]. The methylation of H3K79 is carried out by the histone methylase Dot1L, which exclusively methylates this lysine, and its methylation is increased in actively transcribing genes [6,7]. The inhibition of Dot1l by pinometostat (EPZ) treatment or by Dot1L silencing, stimulated influenza and vesicular stomatitis virus replication [5]. Further characterization showed decreased nuclear translocation of the NF-kB complex, as well as IFN-β, Mx1 and ISG56 expression in EPZ-treated cells [5] indicating a decreased antiviral type I IFN response, and as a consequence, a stimulation in viral replication. Conversely, Dot1L overexpression reduced the multiplication of the virus [8].Invading viral RNAs are detected by different cytoplasmic sensors that promote type I IFN responses to elicit an antiviral state. Among the cytoplasmic RNA sensors, RIG-I plays a pivotal role in the recognition of negative-strand RNA viruses [9,10]. The melanoma differentiation-associated protein 5 (MDA5), has been involved in the recognition of the RNA of picornaviruses [11]. However, some viruses appear to be sensed by both . A...

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Section: Ns1 Protein Modulates the Dot1l Control Of Rig-i-mavs Associsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 97%

Interferon-β Stimulation Elicited by the Influenza Virus Is Regulated by the Histone Methylase Dot1L through the RIG-I-TRIM25 Signaling Axis

Marcos-Villar

Zamarreño

Garaigorta

et al. 2020

Cells

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“…Transcriptomic and proteomic studies have shown the profound impact of HRSV on the physiology of respiratory epithelial cells, its main targets for infection. However, most of those studies have focused on the early innate immune response elicited in the infected cells [12][13][14]. Although, changes in other aspects of the virus-host cell interactions have also been reported, including those involving cell growth, cytoskeleton organization and mitochondrial electron transport [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Metabolic changes during respiratory syncytial virus infection of epithelial cells

et al. 2020

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Viral infections induce substantial metabolic changes in infected cells to optimize viral production while cells develop countermeasures to restrict that infection. Human respiratory syncytial virus (HRSV) is an infectious pathogen that causes severe lower respiratory tract infections (LRTI) in infants, the elderly, and immunocompromised adults for which no effective treatment or vaccine is currently available. In this study, variations in metabolite levels at different time points post-HRSV infection of epithelial cells were studied by untargeted metabolomics using liquid chromatography/mass spectrometry analysis of methanol cell extracts. Numerous metabolites were significantly upregulated after 18 hours post-infection, including nucleotides, amino acids, amino and nucleotide sugars, and metabolites of the central carbon pathway. In contrast, most lipid classes were downregulated. Additionally, increased levels of oxidized glutathione and polyamines were associated with oxidative stress in infected cells. These results show how HRSV infection influences cell metabolism to produce the energy and building blocks necessary for virus reproduction, suggesting potential therapeutic interventions against this virus.

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“…Previous reports have suggested that RIG‐I is a critical immune receptor in infection with the bacterium that possesses immunostimulatory lipopolysaccharide in the early stage 22 . The IFN response is the primary defense system by viral pathogens 23 .…”

Section: Discussionmentioning

confidence: 99%

Yersinia YopT inhibits RLH‐mediated NF‐κB and IRF3 signal transduction

Wang

Zhang

et al. 2020

Microbiology and Immunology

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The Gram-negative bacterial pathogen Yersinia delivers six effector proteins into the host cells to block the host innate immune response. One of the effectors, YopT, is a potent cysteine protease that causes the disruption of the actin cytoskeleton to inhibit phagocytosis of the pathogen; however, its molecular mechanism and relevance to pathogenesis need further investigation. In this report, we show that RIG-I is a novel target of the YopT protein. Remarkably, YopT interacts with RIG-I and inhibits rat liver homogenatemediated nuclear factor-κB and interferon regulatory factor-3 activation. Further studies revealed a YopT-dependent increase in the K48-polymerized ubiquitination of RIG-I. These findings suggest that YopT negatively regulates RIG-I-mediated cellular antibacterial response by targeting RIG-I.

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Apoptosis, Toll-like, RIG-I-like and NOD-like Receptors Are Pathways Jointly Induced by Diverse Respiratory Bacterial and Viral Pathogens

Cited by 24 publications

References 93 publications

Interferon-β Stimulation Elicited by the Influenza Virus Is Regulated by the Histone Methylase Dot1L through the RIG-I-TRIM25 Signaling Axis

Interferon-β Stimulation Elicited by the Influenza Virus Is Regulated by the Histone Methylase Dot1L through the RIG-I-TRIM25 Signaling Axis

Metabolic changes during respiratory syncytial virus infection of epithelial cells

Yersinia YopT inhibits RLH‐mediated NF‐κB and IRF3 signal transduction

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