Modulation of Adaptive Immunity and Viral Infections by Ion Channels

Abstract

Most cellular functions require of ion homeostasis and ion movement. Among others, ion channels play a crucial role in controlling the homeostasis of anions and cations concentration between the extracellular and intracellular compartments. Calcium (Ca2+) is one of the most relevant ions involved in regulating critical functions of immune cells, allowing the appropriate development of immune cell responses against pathogens and tumor cells. Due to the importance of Ca2+ in inducing the immune response, some viruses have evolved mechanisms to modulate intracellular Ca2+ concentrations and the mobilization of this cation through Ca2+ channels to increase their infectivity and to evade the immune system using different mechanisms. For instance, some viral infections require the influx of Ca2+ through ionic channels as a first step to enter the cell, as well as their replication and budding. Moreover, through the expression of viral proteins on the surface of infected cells, Ca2+ channels function can be altered, enhancing the pathogen evasion of the adaptive immune response. In this article, we review those ion channels and ion transporters that are essential for the function of immune cells. Specifically, cation channels and Ca2+ channels in the context of viral infections and their contribution to the modulation of adaptive immune responses.

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

“…The influenza B virus viroporin proton channel is pH-gated and mediates virus uncoating when activated by acidic pH [ 358 ]. Ionic imbalances in cells affecting the homeostasis of cations, including calcium (Ca 2+ ), magnesium (Mg 2+ ), zinc (Zn 2+ ), potassium (K + ), and sodium (Na + ), can interfere with innate and adaptive immunity that affect the pathogenicity of viruses [ 307 , 359 , 360 , 361 ].…”

Comparative Transcriptomics in Atlantic Salmon Head Kidney and SHK-1 Cell Line Exposed to the Sea Louse Cr-Cathepsin

“…The GO classification in common DEGs showed a molecular functions enrichment associated with metal ion binding and catalytic activity. Ions play a crucial role in different physiological aspects, specifically in the immune system cells, where they must maintain strict homeostasis [ 54 , 55 ]. Ion channels and transporters regulate ion concentrations inside T and B cells, and thus could be modulating the functions of these cells [ 56 , 57 ].…”

Computational Analysis of Short Linear Motifs in the Spike Protein of SARS-CoV-2 Variants Provides Possible Clues into the Immune Hijack and Evasion Mechanisms of Omicron Variant

“…The viral proteins expressed on the surface of the infected cells are capable of perturbing intracellular Ca 2+ homeostasis in several ways [ 36 ]. In Omicron-infected cells, an elevated Ca 2+ in the cytoplasm expedites the Ca 2+ /CaM-mediated bridging of the two viral motifs, LIG_CaM_NSCaTE_8 and LIG_CaM_IQ_9, a mechanism analogous to the Cav1 calcium channels where NSCaTE interacts with Ca 2+ /CaM prebound to an IQ domain peptide [ 24 ].…”