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

• Published in: The international journal of biochemistry & cell biology 2020-05, Vol.122, p.105738-105738, Article 105738
• Main Authors: Farag, N.S., Breitinger, U., Breitinger, H.G., El Azizi, M.A.
• Format: Article
• Language: English
• Subjects: Animals; Humans; Immunity, Innate; Inflammasomes; Inflammasomes - immunology; Inflammasomes - metabolism; Inflammation; Inflammation - immunology; Inflammation - metabolism; Inflammation - virology; NLRP3; Review; Toll-Like Receptors - immunology; Toll-Like Receptors - metabolism; Viral Proteins - immunology; Viral Proteins - metabolism; Viroporins; Virus Diseases - immunology; Virus Diseases - metabolism; Virus-immunity; Viruses - immunology; Viruses - metabolism
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2020.105738

•The article provides a summary on cellular receptors involved in virus immunity.•It summarizes key findings on viroporins, a novel class of viral proteins and their role in the virus life cycle and host cell interactions.•It presents an overview of the current understanding of inflammasomes complex activation, with special focus on NLRP3.•It discusses the correlation between viroporins and inflammasomes activation and aggravated inflammatory cytokines production. 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. Inflammasomes are large multimolecular complexes best recognized for their ability to control activation of caspase-1, which in turn regulates the maturation of interleukin-1 β (IL-1β) and interleukin 18 (IL-18). IL-1β was originally identified as a pro-inflammatory cytokine able to induce both local and systemic inflammation and a febrile reaction in response to infection or injury. Excessive production of IL-1β is associated with autoimmune and inflammatory diseases. Microbial derivatives, bacterial pore-forming toxins, extracellular ATP and other pathogen-associated molecular patterns trigger activation of NLRP3 inflammasomes. Recent studies have reported that viroporin activity is capable of inducing inflammasome activity and production of IL-1β, where NLRP3 is shown to be regulated by fluxes of K+, H+ and Ca2+ in addition to reactive oxygen species, autophagy and endoplasmic reticulum stress. The aim of this review is to present an overview of the key findings on viroporin activity with special emphasis on their role in virus immunity and as possible activators of inflammasomes.