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

Highlights

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  The article provides a summary on cellular receptors involved in virus immunity.

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  It presents an overview of the current understanding of inflammasomes complex activation, comparing its different types with special focus on NLRP3.

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  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.

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  The article sheds the light on the correlation between viroporins and inflammasomes activation and their possible contribution to aggravated inflammatory cytokines production.

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  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. 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 Ca ²⁺ 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.