NLRP9b: a novel RNA-sensing inflammasome complex

Ngo, Chinh; Man, Si Ming

doi:10.1038/cr.2017.93

Cited by 11 publications

(9 citation statements)

References 10 publications

(9 reference statements)

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“…A recent study demonstrated possible antiviral implications of pyroptosis downstream of a cross-talk between RV and NLR inflammasome within infected cells [ 153 ]. The inflammasome is a complex of cytosolic proteins which aggregate to mediate proteolytic processing of pro-IL-1β and pro-IL-18 and the pore-forming protein gasdermin D, leading to pyroptosis that liberates biologically active IL-1β and IL-18 from the cell [ 182 ]. Mechanistically, the NLR Nlrp9b was found to recognize short dsRNA stretches (of RV) in an RNA helicase Dhx9-dependent way to form inflammasome complexes with the adaptor proteins Apoptosis-associated speck-like protein containing a CARD (Asc) and caspase-1 leading to IL-18 maturation and gasdermin D-induced pyroptosis.…”

Section: Evasion Of Antiviral Innate Immune Responsementioning

confidence: 99%

Treading a HOSTile path: Mapping the dynamic landscape of host cell–rotavirus interactions to explore novel host-directed curative dimensions

et al. 2021

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Viruses are intracellular pathogens and are dependent on host cellular resources to carry out their cycles of perpetuation. Obtaining an integrative view of host–virus interaction is of utmost importance to understand the complex and dynamic interplay between viral components and host machineries. Besides its obvious scholarly significance, a comprehensive host–virus interaction profile also provides a platform where from host determinants of pro-viral and antiviral importance can be identified and further be subjected to therapeutic intervention. Therefore, adjunct to conventional methods of prophylactic vaccination and virus-directed antivirals, this host-targeted antiviral approach holds promising therapeutic potential. In this review, we present a comprehensive landscape of host cellular reprogramming in response to infection with rotavirus (RV) which causes profuse watery diarrhea in neonates and infants. In addition, an emphasis is given on how host determinants are either usurped or subverted by RV in course of infection and how therapeutic manipulation of specific host factors can effectively modulate the RV life cycle.

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Section: Evasion Of Antiviral Innate Immune Responsementioning

confidence: 99%

Treading a HOSTile path: Mapping the dynamic landscape of host cell–rotavirus interactions to explore novel host-directed curative dimensions

et al. 2021

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“…Significantly, no cells with filaments could be detected, thereby supporting our in vitro findings (Figs 2 and 4B). Since NLRP9-dependent inflammasomes have been studied more extensively in the murine system [20][21][22], we also tested filament formation for murine NLRP9b PYD fusion protein overexpressed in HEK293T cells. Given its relatively low sequence identity of 52.1% with human NLRP9 PYD (murine 1-91 versus human 1-94), we found it reasonable to anticipate murine NLRP9 PYD to potentially form filaments.…”

Section: Nlrp9 Pyd Does Not Self-polymerize Nor Nucleate Asc Speck Fomentioning

confidence: 99%

“…A less studied member of the NLRP subfamily is NLRP9, which was first described as a maternal effect gene in bovine [16][17][18][19]. Upon recognition of low molecular weight dsRNA by the endogenous RNA helicase DHX9, its mouse analogue NLRP9b was described to form an inflammasome with ASC and caspase-1 [20,21]. This inflammasomal complex mediates pyroptosis of intestinal epithelial cells (IECs), thereby limiting rotaviral replication in mice [20,21].…”

mentioning

confidence: 99%

“…Upon recognition of low molecular weight dsRNA by the endogenous RNA helicase DHX9, its mouse analogue NLRP9b was described to form an inflammasome with ASC and caspase-1 [20,21]. This inflammasomal complex mediates pyroptosis of intestinal epithelial cells (IECs), thereby limiting rotaviral replication in mice [20,21]. Additionally, NLRP9b deficiency resulted in less pulmonary histopathological alterations in a mouse model of acute lung injury and markedly elevated proinflammatory cytokine and chemokine levels, as well as ROS production, in a LPS-activated mouse epithelial cell line [22].…”

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Crystal structure of the human NLRP9 pyrin domain suggests a distinct mode of inflammasome assembly

et al. 2020

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Inflammasomes are cytosolic multimeric signaling complexes of the innate immune system that induce activation of caspases. The NOD-like receptor NLRP9 recruits the adaptor protein ASC to form an ASC-dependent inflammasome to limit rotaviral replication in intestinal epithelial cells, but only little is known about the molecular mechanisms regulating and driving its assembly. Here, we present the crystal structure of the human NLRP9 pyrin domain (PYD). We show that NLRP9 PYD is not able to self-polymerize nor to nucleate ASC specks in HEK293T cells. A comparison with filament-forming PYDs revealed that NLRP9 PYD adopts a conformation compatible with filament formation, but several charge inversions of interfacing residues might cause repulsive effects that prohibit self-oligomerization. These results propose that inflammasome assembly of NLRP9 might differ largely from what we know of other inflammasomes.

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“…DExH‐box helicase (DHX)9, an RNA helicase that preferentially bound to short dsRNA, was proposed as the intermediate protein bringing NLRP9b and viral RNA into the same complex 25 . How DHX9 distinguishes between viral RNA and host RNA to avoid triggering autoinflammatory response in this context is still not fully understood 30 . Moreover, the exact molecular mechanisms underlying NLRP9b inflammasome formation still require further dissection.…”

Section: Molecular and Structural Mechanisms Of Nlrp9 Activationmentioning

confidence: 99%

NLRP9 in innate immunity and inflammation

Mullins

Chen

2020

Immunology

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NLRP9, one of the less‐characterized NLR members, has been shown to initiate inflammasome activation in host defence against rotavirus infection. This review highlights the latest progress in characterization of the role of NLRP9 in infectious and inflammatory diseases. The recent crystallographic and biochemical studies on NLRP9 have also raised some important questions remained to be fully investigated.

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NLRP9b: a novel RNA-sensing inflammasome complex

Cited by 11 publications

References 10 publications

Treading a HOSTile path: Mapping the dynamic landscape of host cell–rotavirus interactions to explore novel host-directed curative dimensions

Treading a HOSTile path: Mapping the dynamic landscape of host cell–rotavirus interactions to explore novel host-directed curative dimensions

Crystal structure of the human NLRP9 pyrin domain suggests a distinct mode of inflammasome assembly

NLRP9 in innate immunity and inflammation

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