Zika virus elicits inflammation to evade antiviral response by cleaving
            <scp>cGAS</scp>
            via
            <scp>NS</scp>
            1‐caspase‐1 axis

Zheng, Yanyan; Liu, Qingxiang; Wu, Yiming; Ma, Ling; Zhang, Zhenzhen; Liu, Tao; Jin, Shouheng; She, Yuanchu; Li, Yiping; Cui, Jun

doi:10.15252/embj.201899347

Cited by 159 publications

(142 citation statements)

References 48 publications

(78 reference statements)

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“…The ZIKV infection is a public health emergency and host IFN-β-associated antiviral innate immunity is essential for the control of this viral infection. Zheng and colleagues discovered that ZIKV infection induces NLRP3 inflammasome activation and deliberately enhances its activation through the NS1 protein (75). NS1 recruits the host deubiquitinase, USP8, to cleave the polyubiquitin chains from caspase-1 so as to inhibit the proteasomal degradation of caspase-1 and, subsequently, amplify the NLRP3 activation signal.…”

Section: Viral Evasion Strategies Targeting the Nlrp3 Inflammasomementioning

confidence: 99%

NLRP3 Inflammasome—A Key Player in Antiviral Responses

2020

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The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is an oligomeric complex comprised of the NOD-like receptor NLRP3, the adaptor ASC, and caspase-1. This complex is crucial to the host's defense against microbes as it promotes IL-1β and IL-18 secretion and induces pyroptosis. NLRP3 recognizes variety of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) generated during viral replication that triggers the NLRP3 inflammasome-dependent antiviral immune responses and facilitates viral eradication. Meanwhile, several viruses have evolved elaborate strategies to evade the immune system by targeting the NLRP3 inflammasome. In this review, we will focus on the crosstalk between the NLRP3 inflammasome and viruses, provide an overview of viral infection-induced NLRP3 inflammasome activation, and the immune escape strategies of viruses through their modulation of the NLRP3 inflammasome activity.

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Section: Viral Evasion Strategies Targeting the Nlrp3 Inflammasomementioning

confidence: 99%

NLRP3 Inflammasome—A Key Player in Antiviral Responses

2020

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“…Another study showed that the inflammasome can decrease the IFN response and support viral replication [148]. This was established using Nlrp3 -/neonatal mice (Nlrp3 plays a role in inflammasome activation) that were injected with ZIKV in the brain.…”

Section: Innate Immune Evasion and Flavivirus Pathogenesismentioning

confidence: 99%

Viral Innate Immune Evasion and the Pathogenesis of Emerging RNA Virus Infections

Nelemans

Kikkert

2019

Preprint

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Positive-sense single-stranded RNA (+ssRNA) viruses comprise many (re-)emerging human pathogens that pose a public health problem. Our innate immune system and in particular the interferon response form the important first line of defense against these viruses. Given their genetic flexibility, these viruses have therefore developed multiple strategies to evade the innate immune response in order to optimize their replication capacity. Already many molecular mechanisms of innate immune evasion by +ssRNA viruses have been identified. However, research addressing the effect of host innate immune evasion on the pathology caused by the viral infection is less prevalent in literature, though very relevant and interesting. Since interferons have been implicated in inflammatory diseases and immunopathology in addition to their protective role in infection, the influence of antagonizing the immune response may have an ambiguous effect on the clinical outcome of the viral disease. Therefore, this review discusses what is currently known about the role of interferons and host immune evasion in the pathogenesis of emerging viruses belonging to the coronaviruses, alphaviruses and flaviviruses.

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“…[26][27][28] HEK293T cells were co-transfected with plasmids encoding p3XFlag-NLRP3, pEGFP-C1-ASC, pCI-Casp-1-HA and pEGFP-C1-IL-1β. To test this, we established an in vitro IL-1β cleavage cell system in HEK293T cells, in which the NLRP3 inflammasome is deficient and can be reconstituted.…”

Section: Ginsenoside Rg3 Blocks Nek7-nlrp3 Interactionmentioning

confidence: 99%

Ginsenoside Rg3 suppresses the NLRP3 inflammasome activation through inhibition of its assembly

et al. 2019

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Ginsenoside Rg3 is one of the main constituents of Panax ginseng. Compelling evidence has demonstrated that ginsenoside Rg3 is capable of inhibiting inflammation.However, the mechanism mediating its anti-inflammatory effects remain unclear.Here we show that ginsenoside Rg3 blocks IL-1β secretion and caspase-1 activation through inhibiting LPS priming and the NLRP3 inflammasome activation in human and mouse macrophages. Rg3 specifically inhibits activation of NLRP3 but not the NLRC4 or AIM2 inflammasomes. In addition, Rg3 has no effect on upstream regulation of NLRP3 inflammasome, such as K + efflux, ROS production, or mitochondrial membrane potential. Mechanistically, Rg3 abrogates NEK7-NLRP3 interaction, and subsequently inhibits NLRP3-ASC interaction, ASC oligomerization, and speckle formation. More importantly, Rg3 can reduce IL-1β secretion induced by LPS in mice and protect mice from lethal endotoxic shock. Thus, our findings reveal an anti-inflammatory mechanism for Rg3 and suggest its potential use in NLRP3-driven diseases. K E Y W O R D Santi-inflammation, ginsenoside Rg3, inflammasome, NLRP3 inflammasome | 209 SHI et al. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.

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Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS 1‐caspase‐1 axis

Cited by 159 publications

References 48 publications

NLRP3 Inflammasome—A Key Player in Antiviral Responses

NLRP3 Inflammasome—A Key Player in Antiviral Responses

Viral Innate Immune Evasion and the Pathogenesis of Emerging RNA Virus Infections

Ginsenoside Rg3 suppresses the NLRP3 inflammasome activation through inhibition of its assembly

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