Stimulation of Innate Immunity by Host and Viral RNAs

Streicher, Félix; Jouvenet, Nolwenn

doi:10.1016/j.it.2019.10.009

Cited by 87 publications

(67 citation statements)

References 93 publications

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“…Type I interferon (IFN-I) response is critical for providing an efficient protection against viral infections. IFN-I production is rapidly triggered by the recognition by host sensors of pathogen-associated molecular patterns (PAMPs), such as viral nucleic acids [6]. IFN-I-induced signaling converges on transcription factors, which rapidly induces the expression of hundreds of genes called interferon-stimulated genes (ISGs) (reviewed in [7,8]).…”

Section: Plos Pathogensmentioning

confidence: 99%

Interplay between SARS-CoV-2 and the type I interferon response

et al. 2020

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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. An unbalanced immune response, characterized by a weak production of type I interferons (IFN-Is) and an exacerbated release of proinflammatory cytokines, contributes to the severe forms of the disease. SARS-CoV-2 is genetically related to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused outbreaks in 2003 and 2013, respectively. Although IFN treatment gave some encouraging results against SARS-CoV and MERS-CoV in animal models, its potential as a therapeutic against COVID-19 awaits validation. Here, we describe our current knowledge of the complex interplay between SARS-CoV-2 infection and the IFN system, highlighting some of the gaps that need to be filled for a better understanding of the underlying molecular mechanisms. In addition to the conserved IFN evasion strategies that are likely shared with SARS-CoV and MERS-CoV, novel counteraction mechanisms are being discovered in SARS-CoV-2-infected cells. Since the last coronavirus epidemic, we have made considerable progress in understanding the IFN-I response, including its spatiotemporal regulation and the prominent role of plasmacytoid dendritic cells (pDCs), which are the main IFN-I-producing cells. While awaiting the results of the many clinical trials that are evaluating the efficacy of IFN-I alone or in combination with antiviral molecules, we discuss the potential benefits of a well-timed IFN-I treatment and propose strategies to boost pDC-mediated IFN responses during the early stages of viral infection.

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Section: Plos Pathogensmentioning

confidence: 99%

Interplay between SARS-CoV-2 and the type I interferon response

et al. 2020

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“…Thus, we need to better characterize the pathway leading to H1 proteolysis in senescence so that we can restore H1 levels and test its effect on ISG expression. The innate immunity proteins that recognize repeat RNAs in senescence must also be identified (49).…”

Section: Discussionmentioning

confidence: 99%

The H2A.J histone variant contributes to Interferon-Stimulated Gene expression in senescence by its weak interaction with H1 and the derepression of repeated DNA sequences

Mangelinck

Coudereau

Courbeyrette

et al. 2020

Preprint

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The histone variant H2A.J was previously shown to accumulate in senescent human fibroblasts with persistent DNA damage to promote inflammatory gene expression, but its mechanism of action was unknown. We show that H2A.J accumulation contributes to weakening the association of histone H1 to chromatin and increasing its turnover. Decreased H1 in senescence is correlated with increased expression of some repeated DNA sequences, increased expression of STAT/IRF transcription factors, and transcriptional activation of Interferon-Stimulated Genes (ISGs). The H2A.J-specific Val-11 moderates the transcriptional activity of H2A.J, and H2A.J-specific Ser-123 can be phosphorylated in response to DNA damage with potentiation of its transcriptional activity by the phospho-mimetic S123E mutation. Our work demonstrates the functional importance of H2A.J-specific residues and potential mechanisms for its function in promoting inflammatory gene expression in senescence.

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“…Based on their structures, locations, and functional specificities, PRRs are separated into discrete families, which include the membrane bound Toll-like receptors (TLRs), the cytosolic nucleotide-binding oligomerization domain (NOD)like receptors (NLRs), cyclic GMP-AMP (cGAMP) synthase (cGAS), and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) (Kawai and Akira, 2011;Franchi et al, 2012;Streicher and Jouvenet, 2019). The activity of these PRRs has been described to be influenced at various levels by mitochondria.…”

Section: Innate Immunity and Mitochondriamentioning

confidence: 99%

Mitochondrial Interactome: A Focus on Antiviral Signaling Pathways

Refolo

Vescovo

Piacentini

et al. 2020

Front. Cell Dev. Biol.

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In the last years, proteomics has represented a valuable approach to elucidate key aspects in the regulation of type I/III interferons (IFNs) and autophagy, two main processes involved in the response to viral infection, to unveil the molecular strategies that viruses have evolved to counteract these processes. Besides their main metabolic roles, mitochondria are well recognized as pivotal organelles in controlling signaling pathways essential to restrain viral infections. In particular, a major role in antiviral defense is played by mitochondrial antiviral signaling (MAVS) protein, an adaptor protein that coordinates the activation of IFN inducing pathways and autophagy at the mitochondrial level. Here, we provide an overview of how mass spectrometry-based studies of protein-protein interactions and post-translational modifications (PTMs) have fostered our understanding of the molecular mechanisms that control the mitochondriamediated antiviral immunity.

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Stimulation of Innate Immunity by Host and Viral RNAs

Cited by 87 publications

References 93 publications

Interplay between SARS-CoV-2 and the type I interferon response

Interplay between SARS-CoV-2 and the type I interferon response

The H2A.J histone variant contributes to Interferon-Stimulated Gene expression in senescence by its weak interaction with H1 and the derepression of repeated DNA sequences

Mitochondrial Interactome: A Focus on Antiviral Signaling Pathways

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