Activation and Inhibition of the NLRP3 Inflammasome by RNA Viruses

Abstract

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.

Pyroptosis: A New Regulating Mechanism in Cardiovascular Disease

“…On the other hand, some viruses use virally encoded proteins to inhibit inflammatory activation, such as the influenza virus NS1 protein and the measles virus (MV) V protein. 44 …”

The Crucial Role of NLRP3 Inflammasome in Viral Infection-Associated Fibrosing Interstitial Lung Diseases

“…Overall, various RNA viruses can activate the NLRP3 inflammasomes via ROS-dependent pathway, rupture lysosomes, the Golgi network, cathepsin B-dependent process, MFN2, Ca 2+ model, and K + model involving pannexin-1 and P2X purinoceptor 7 (P2X7) channels [ 65 ]. Furthermore, mechanisms of virus-mediated NLRP3 activation through viral RNA (single-stranded RNA (ssRNA) or dsRNA) depending on the type of virus and by viroporin proteins, which induce ion efflux from intracellular storage into the cytosol [ 58 ].…”

“…A decrease in intracellular K + concentration was identified as the common trigger of NLRP3 inflammasome activation in response to ATP, nigericin, particulate molecules, crystalline, small chemical compounds, such as GB111-NH2, imiquimod, and CL097, NLRP3-activating mutations, and signals from the alternative inflammasome pathway [ 45 ]. Lower and higher concentrations of cytosolic K + will induce and block the activation of the NLRP3 inflammasome via a mechanism that is still not well understood [ 65 ].…”

“…Murine norovirus (MNV) leads to GSDSD dependent pyroptosis resulting in NLRP3 activation exhibited elevated MAVS-mediated IL-1β secretion. Also, MFN2 is required for NLRP3 activation after infection with RNA viruses, such as influenza, measles, or encephalomyocarditis virus (EMCV) [ 65 ].…”

“…PAMPs and DAMPs of viral origin and NLRP3 activators, including nigericin, asbestos, silica, alum, and amyloid β, form aggregates that are phagocytosed resulting in the disruption of lysosomes and the consequent release of lysosomal components, especially cathepsin B [ 58 ]. Influenza viruses use rupture lysosomes and then activate NLRP3 inflammasomes via a cathepsin B-dependent processes; however, the function of these events remains an open question in NLRP3 activation [ 65 ].…”