Viroporins and inflammasomes: A key to understand virus-induced inflammation

Abstract

J o u r n a l P r e -p r o o f Highlights  The article provides a summary on cellular receptors involved in virus immunity.  It presents an overview of the current understanding of inflammasomes complex activation, comparing its different types with special focus on NLRP3.  The article summarizes key findings on viroporins, a novel class of viral proteins and their role in the virus life cycle and host cell interactions.  The article sheds the light on the correlation between viroporins and inflammasomes activation and their possible contribution to aggravated inflammatory cytokines production.  The article proposes targeting inflammasomes in combination with viroporin inhibitors in virus-induced disease as an emerging attractive therapeutic option. Abstract Viroporins are virus encoded proteins that alter membrane permeability and can trigger subsequent cellular signals. Oligomerization of viroporin subunits results in formation of a hydrophilic pore which facilitates ion transport across host cell membranes. These viral channel proteins may be involved in different stages of the virus infection cycle. J o u r n a l P r e -p r o o f List of abbreviationsAIM Absent in melanoma ASC Apoptosis-associated speck-like protein containing a carboxy-terminal CARD ATP Adenosine triphosphate BMDC Bone marrow derived dendritic cells BMM Bone marrow derived macrophages CARD Caspase activation and recruitment domain CD Cluster of differentiation CoV Coronavirus CSFV Classical swine fever virus DAMPs Danger associated molecular patterns DC Dendritic cells EMCV Encephalomyocarditis virus HCV Hepatitis C virus HIV Human immune deficiency virus LPS Lipopolysaccharide LRR Leucine rich repeats MAL MyD88-adaptor-like MAM Mitochondrial-associated membrane MAVS Mitochondrial antiviral signaling protein MDA5 Melanoma differentiation-associated protein 5 MERS Middle East respiratory syndrome-related coronavirus MHC Major histocompatibility complex J o u r n a l P r e -p r o o f MSU Monosodium urate MyD88 Myeloid differentiation primary response 88 NADPH Nicotinamide adenine dinucleotide phosphate NALP NACHT, LRR and PYD domains-containing protein NFκB Nuclear factor kappa b NLR Nucleotide-binding domain, leucine-rich repeat NLRP3 NLR family, pyrin domain containing 3 Nod Nucleotide oligomerization domain PAMP Pathogen associated molecular patterns PRR Pattern recognition receptors PYD Pyrin domain RIG-1 Retinoic acid-inducible gene I RLR RIG-1 like receptor ROS Reactive Oxygen species RSV Respiratory syncytial virus

The Role of NLRP3 Inflammasome in the Pathogenesis of Traumatic Brain Injury

“…Complications such as continuous stimuli or infections, such as viral infections, may worsen the prognosis of TBI, altering the immune response and increasing the related neuroinflammatory processes. Viral infections are often related to inflammation and virus proteins, as viroporins, may play a pivotal role in promoting viral infection [ 142 ]. Previous studies showed that viroporins promote NLRP3 inflammasome activation [ 142 , 143 ], in fact NLRP3 activation was observed following influenza A virus and SARS-CoV infections [ 144 ].…”

“…Viral infections are often related to inflammation and virus proteins, as viroporins, may play a pivotal role in promoting viral infection [ 142 ]. Previous studies showed that viroporins promote NLRP3 inflammasome activation [ 142 , 143 ], in fact NLRP3 activation was observed following influenza A virus and SARS-CoV infections [ 144 ]. In the past few months and until now, a novel coronavirus, the SARS-CoV-2, is affecting the population worldwide, thus causing a high number of deaths so that the World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) as global pandemic.…”

Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19?

“…Generated via the activation of the NLRP3 inflammasome, a multi-subunit complex comprising of the NLR protein NLRP3, the adaptor protein ASC and caspase-1, IL-1β promotes anti-microbial resistance via the modulation of innate and adaptive immune responses ( 65 ). However, if dysregulated, production of this pro-inflammatory cytokine can promote lung injury and severe pulmonary fibrosis ( 66 , 67 ).…”

PNPLA3 and TLL-1 polymorphisms affect disease severity in patients with COVID-19

“…The PNPLA3 missense variant rs738409Ile148Met) (C>G), causing loss of function, is associated with hyperexpression of the NLRP3 in ammosome, leading to increased serum levels of IL-1β and IL18 [18]. It is known that many viruses and among them SARS-CoV-2, are directly able to induce activation of the NRLP3 in ammosome leading to the cytokines storm probably causing most fatal outcomes [19]. In our subcohort of patients ≤65 years, the GG PNPLA3 genotype was signi cantly associated to an increased risk of severe outcome.…”

“…Albeit the pathogenetic mechanism of coronavirus disease 2019 (COVID- 19) is yet partly unclear, the course and outcome of disease seem to be signi cantly in uenced by host factors supporting a strong proin ammatory response and inducing a massive release of cytokines leading to a "cytokine storm" ultimately causing severe alveolar damage but also multiorgan failure [4]. It is thus conceivable that the complexity of host genetic background in terms of polymorphisms in genes involved in SARS-CoV-2 receptor-dependent endocytosis, antiviral responses and modulation of cell infection and reinfection, in ammation, or immune stimulation may play a key role in pathogenesis and outcome of COVID-19.…”