Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome

Cheong, Woo Chang; Kang, Hye Ri; Yoon, Hye Sun; Kang, Sang-Won; Ting, Jenny P.‐Y.; Song, Mee Hyun

doi:10.1371/journal.pone.0126456

Cited by 66 publications

(60 citation statements)

References 47 publications

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“…Although this review is focused on skin immunity, it is noteworthy and in agreement with this hypothesis that IL-36a plays an essential role in initiating immune responses against influenza (120). The influenza protein NS1 (nonstructural protein 1) blocks NLRP3 function (134,135), similar to inflammasome inhibition by other viruses, as described above.…”

Section: Viral Immune Evasion and Potential Counteraction By Il-36supporting

confidence: 57%

Interleukin-36 cytokines may overcome microbial immune evasion strategies that inhibit interleukin-1 family signaling

Jensen

2017

Sci. Signal.

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Pathogens deploy immune evasion strategies to successfully establish infections within their hosts. Naturally, the host responds by acquiring mechanisms to counter these strategies. There is increasing evidence that the three interleukin-36 (IL-36) cytokines, IL-36a, IL-36b and IL-36g, play important roles in host immunity. With a focus on the skin as a target for microbial and viral invasion, the current knowledge of IL-36 functions is reviewed. Furthermore, the hypothesis that the IL-36s have evolved to counteract virulence factors is presented using viruses as an example. The IL-36s are related to IL-1a, IL-1b, IL-18, and IL-33. Numerous viruses affecting the skin have developed immune evasion strategies that neutralize IL-1a, IL-1b, or IL-18 signaling or combinations of these pathways. Through small differences in activation mechanisms and receptor utilization, it is possible that IL-36 signaling may proceed unhindered in the presence of these viral inhibitors. Thus, one physiological function of the IL-36s may be to counteract microbial immune evasion.

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Section: Viral Immune Evasion and Potential Counteraction By Il-36supporting

confidence: 57%

Interleukin-36 cytokines may overcome microbial immune evasion strategies that inhibit interleukin-1 family signaling

Jensen

2017

Sci. Signal.

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“…These findings suggest that influenza virus NS1 protein targets both the NLRP3 and NF-jB, thus abrogating inflammasome activation, as a viral immune evasion strategy [148]. In conclusion, current evidence of new viral proteins that regulate the innate immune response specifically with regard to inflammasome activation is a critical issue that is gaining momentum.…”

Section: Inhibition Of Caspase-1mentioning

confidence: 94%

Inflammasomes and its importance in viral infections

León-Juárez²,

et al. 2016

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A complex interplay between pathogen and host determines the immune response during viral infection. A set of cytosolic sensors are expressed by immune cells to detect viral infection. NOD-like receptors (NLRs) comprise a large family of intracellular pattern recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed inflammasomes, which induce downstream immune responses to specific pathogens, environmental stimuli, and host cell damage. Inflammasomes are composed of cytoplasmic sensor molecules such as NLRP3 or absent in melanoma 2 (AIM2), the adaptor protein ASC (apoptosis-associated speck-like protein containing caspase recruitment domain), and the effector protein procaspase-1. The inflammasome operates as a platform for caspase-1 activation, resulting in caspase-1-dependent proteolytic maturation and secretion of interleukin (IL)-1b and IL-18. This, in turn, activates the expression of other immune genes and facilitates lymphocyte recruitment to the site of primary infection, thereby controlling invading pathogens. Moreover, inflammasomes counter viral replication and remove infected immune cells through an inflammatory cell death, program termed as pyroptosis. As a countermeasure, viral pathogens have evolved virulence factors to antagonise inflammasome pathways. In this review, we discuss the role of inflammasomes in sensing viral infection as well as the evasion strategies that viruses have developed to evade inflammasome-dependent immune responses. This information summarises our understanding of host defence mechanisms against viruses and highlights research areas that can provide new approaches to interfere in the pathogenesis of viral diseases.

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“…Linking the type I IFN induction system to inflammasome activation, RIG-I contributes to upregulation of NLRP3 inflammasome components through type I IFN signaling, and remarkably, RIG-I can also form a non-canonical inflammasome complex with ASC and caspase-1 [203]. Further highlighting the importance and connectivity of these pathways, the influenza virus NS1 protein directly binds to RIG-I and antagonizes cellular production of both IFNs and IL-1β [189,204–206]. Thus, the viral sensing pathways that lead to type I IFN and IL-1β secretion are interrelated and are both critically involved in anti-influenza virus immunity.…”

Section: Pathogens Differentially Interfere With the Inflammasomes Anmentioning

confidence: 99%

Checks and Balances between Autophagy and Inflammasomes during Infection

Seveau

Turner

Gavrilin

et al. 2018

Journal of Molecular Biology

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Autophagy and inflammasome complex assembly are physiological processes that control homeostasis, inflammation, and immunity. Autophagy is a ubiquitous pathway that degrades cytosolic macromolecules or organelles, as well as intracellular pathogens. Inflammasomes are multi-protein complexes that assemble in the cytosol of cells upon detection of pathogen- or danger-associated molecular patterns. A critical outcome of inflammasome assembly is the activation of the serine protease caspase-1, which activates the pro-inflammatory cytokine precursors pro-IL-1β and pro-IL-18. Studies on chronic inflammatory diseases, heart diseases, Alzheimer's disease, and multiple sclerosis revealed that autophagy and inflammasomes intersect and regulate each other. In the context of infectious diseases, however, less is known about the interplay between autophagy and inflammasome assembly, although it is becoming evident that pathogens have evolved multiple strategies to inhibit and/or subvert these pathways and to take advantage of their intricate crosstalk. An improved appreciation of these pathways and their subversion by diverse pathogens is expected to help in the design of anti-infective therapeutic interventions.

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Influenza A Virus NS1 Protein Inhibits the NLRP3 Inflammasome

Cited by 66 publications

References 47 publications

Interleukin-36 cytokines may overcome microbial immune evasion strategies that inhibit interleukin-1 family signaling

Interleukin-36 cytokines may overcome microbial immune evasion strategies that inhibit interleukin-1 family signaling

Inflammasomes and its importance in viral infections

Checks and Balances between Autophagy and Inflammasomes during Infection

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