Nitric oxide attenuates PI4P accumulation at the ER membrane to inhibit encephalomyocarditis virus replication selectively in β-cells. J Biol Chem 2025 Dec;301(12):110798
Date
10/10/2025Pubmed ID
41067639Pubmed Central ID
PMC12639437DOI
10.1016/j.jbc.2025.110798Scopus ID
2-s2.0-105020808916 (requires institutional sign-in at Scopus site)Abstract
Viral infection, particularly by members of the picornavirus family, has been associated with autoimmune diabetes (type 1 diabetes mellitus) onset. The encephalomyocarditis virus (EMCV) is a mouse-tropic member of the picornavirus family that stimulates innate immune activation, leading to the production of cytokines. In response to cytokines, β-cells express inducible nitric oxide (NO) synthase and produce low micromolar levels of the free radical, NO. We have previously shown that, because of its inhibitory action on mitochondrial oxidation and depletion of cellular ATP, NO selectively attenuates EMCV replication in, and lysis of, β-cells. In this study, we show that one mechanism by which NO inhibits EMCV replication is by attenuating the accumulation of phosphatidylinositol-4-phosphate at the endoplasmic reticulum membrane. As a result, viral replication complex formation is prohibited, and viral replication is effectively prevented. In agreement with previous studies, we show that these observations are selective for β-cells and because of a loss of cellular ATP.
Author List
Gehant AL, Stafford JD, Hansen PA, Harty KR, Naatz A, Corbett JAAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAnimals
Cardiovirus Infections
Encephalomyocarditis virus
Endoplasmic Reticulum
Insulin-Secreting Cells
Mice
Nitric Oxide
Nitric Oxide Synthase Type II
Phosphatidylinositol Phosphates
Virus Replication
