PB1-F2 protein of highly pathogenic influenza A (H7N9) virus selectively suppresses RNA-induced NLRP3 inflammasome activation through inhibition of MAVS-NLRP3 interaction

Cheung, Pak‐Hin Hinson; Ye, Zi‐Wei; Lee, Tak-Wang Terence; Chen, Honglin; Chan, Chi-Ping; Jin, Dong Yan

doi:10.1002/jlb.4ab0420-694r

Cited by 31 publications

(32 citation statements)

References 44 publications

(155 reference statements)

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“…Interestingly, instead of activating NLRP3 inflammasome maturation, intracellularly expressed PB1‐F2 seems to suppress NLRP3 inflammasome activation as demonstrated in NLRP3 inflammasome reconstitution experiment in nonphagocytic cell line HEK293T 41 . We have recently found that intracellular PB1‐F2 suppresses inflammasome in an IAV subtype‐dependent manner, with PB1‐F2 of highly pathogenic IAV being a less potent suppressor than PB1‐F2 of low pathogenicity IAV 66 . This suggests that the ability to activate NLRP3 inflammasome is specific to extracellular PB1‐F2.…”

Section: Extracellular Pb1‐f2—nlrp3 Inflammasome Activation and Necrosismentioning

confidence: 95%

Influenza A virus PB1-F2 protein: An ambivalent innate immune modulator and virulence factor

Cheung

Lee

Chan

et al. 2020

Journal of Leukocyte Biology

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Influenza A virus (IAV) causes not only seasonal respiratory illness, but also outbreaks of more severe disease and pandemics when novel strains emerge as a result of reassortment or interspecies transmission. PB1-F2 is an IAV protein expressed from the second open reading frame of PB1 gene. Small as it is, PB1-F2 is a critical virulence factor. Multiple key amino acid residues and motifs of PB1-F2 have been shown to influence the virulence of IAV in a strain-and host-specific manner, plausibly through the induction of apoptotic cell death, modulation of type I IFN response, activation of inflammasome, and facilitation of secondary bacterial infection. However, the exact role of PB1-F2 in IAV pathogenesis remains unexplained.Through reanalysis of the current literature, we redefine PB1-F2 as an ambivalent innate immune modulator that determines IAV infection outcome through induction of immune cell death, differential modulation of early-and late-type I IFN response, and promotion of pathogenic inflammation. PB1-F2 functions both intracellularly and extracellularly. Further investigations of the mechanistic details of PB1-F2 action will shed new light on immunopathogenesis of IAV infection.

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Section: Extracellular Pb1‐f2—nlrp3 Inflammasome Activation and Necrosismentioning

confidence: 95%

Influenza A virus PB1-F2 protein: An ambivalent innate immune modulator and virulence factor

Cheung

Lee

Chan

et al. 2020

Journal of Leukocyte Biology

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“…156 Again, PB1-F2 protein of highly pathogenic influenza A (H7N9) seized the IL-1β secretion from IAV-infected macrophages resulting the inhibition of RNA-induced NLRP3 inflammasome activation. 157 However, this protein is the subject of debate concerning its pro-inflammatory properties. Another study has shown that extracellular protein aggregate PB1-F2 phagocytose is known for its macrophages contributing 158 It is still unknown how extracellular and intracellular fabricate PB1-F2 contributes to viral pathogenesis.…”

Section: Rna Viruses That Inhibit Nlrp3 Inflammasomes Using Virus-encoded Proteinsmentioning

confidence: 99%

“…Another study has shown that extracellular protein aggregate PB1-F2 phagocytose is known for its macrophages contributing 158 It is still unknown how extracellular and intracellular fabricate PB1-F2 contributes to viral pathogenesis. 157 PYD-containing viral proteins, such as the Shope fibroma virus (SFV)-encoded PYD-only protein/macromolecule (vPOP) and the M13L protein of poxvirus, co-localize and associate with ASC via PYD-PYD interactions and then prevent caspase-1 activation and IL-1β production. 159,160 The NS1 protein of influenza A virus can inhibit the NLRP3 inflammasome, 161 with NS1 proteins from both extremely infective and low-pathogenicity strains dramatically reducing IL-1β and IL-18 secretion by LPS-and ATP-treated THP-1 cells.…”

Section: Rna Viruses That Inhibit Nlrp3 Inflammasomes Using Virus-encoded Proteinsmentioning

confidence: 99%

Activation and Inhibition of the NLRP3 Inflammasome by RNA Viruses

Choudhury¹,

Ma²,

Abdullah³

et al. 2021

JIR

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Inflammation refers to the response of the immune system to viral, bacterial, and fungal infections, or other foreign particles in the body, which can involve the production of a wide array of soluble inflammatory mediators. It is important for the development of many RNA virus-infected diseases. The primary factors through which the infection becomes inflammation involve inflammasome. Inflammasomes are proteins complex that the activation is responsive to specific pathogens, host cell damage, and other environmental stimuli. Inflammasomes bring about the maturation of various pro-inflammatory cytokines such as IL-18 and IL-1β in order to mediate the innate immune defense mechanisms. Many RNA viruses and their components, such as encephalomyocarditis virus (EMCV) 2B viroporin, the viral RNA of hepatitis C virus, the influenza virus M2 viroporin, the respiratory syncytial virus (RSV) small hydrophobic (SH) viroporin, and the human rhinovirus (HRV) 2B viroporin can activate the Nod-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome to influence the inflammatory response. On the other hand, several viruses use virus-encoded proteins to suppress inflammation activation, such as the influenza virus NS1 protein and the measles virus (MV) V protein. In this review, we summarize how RNA virus infection leads to the activation or inhibition of the NLRP3 inflammasome.

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“…The study also showed that the reduction of membrane potential not only suppresses RIG-I signaling, but also blocks NLRP3 inflammasome activation by the co-transfection of inflammasome components in HEK293T cells. Another study further showed that the PB1-F2 of IAV H7N9 selectively suppresses dsRNA-induced NLRP3 inflammasome activation by inhibition of MAVS-NLRP3 interaction [ 119 ]. However, whether PB1-F1 inhibits the activation of inflammasome during viral infection is not clear.…”

Section: Pb1-f2mentioning

confidence: 99%

Roles of the Non-Structural Proteins of Influenza A Virus

Hao

Wang

2020

Pathogens

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Influenza A virus (IAV) is a segmented, negative single-stranded RNA virus that causes seasonal epidemics and has a potential for pandemics. Several viral proteins are not packed in the IAV viral particle and only expressed in the infected host cells. These proteins are named non-structural proteins (NSPs), including NS1, PB1-F2 and PA-X. They play a versatile role in the viral life cycle by modulating viral replication and transcription. More importantly, they also play a critical role in the evasion of the surveillance of host defense and viral pathogenicity by inducing apoptosis, perturbing innate immunity, and exacerbating inflammation. Here, we review the recent advances of these NSPs and how the new findings deepen our understanding of IAV–host interactions and viral pathogenesis.

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PB1-F2 protein of highly pathogenic influenza A (H7N9) virus selectively suppresses RNA-induced NLRP3 inflammasome activation through inhibition of MAVS-NLRP3 interaction

Cited by 31 publications

References 44 publications

Influenza A virus PB1-F2 protein: An ambivalent innate immune modulator and virulence factor

Influenza A virus PB1-F2 protein: An ambivalent innate immune modulator and virulence factor

Activation and Inhibition of the NLRP3 Inflammasome by RNA Viruses

Roles of the Non-Structural Proteins of Influenza A Virus

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