Editor(s)
Ronald C. Wek
Abstract
Viral infection is one environmental factor that may contribute to the initiation of pancreatic b-cell destruction during the development of autoimmune diabetes. Picornaviruses, such as encephalomyocarditis virus (EMCV), induce a pro-inflammatory response in islets leading to local production of cytokines, such as IL-1, by resident islet leukocytes. Furthermore, IL-1 is known to stimulate b-cell expression of iNOS and production of the free radical nitric oxide. The purpose of this study was to determine whether nitric oxide contributes to the b-cell response to viral infection. We show that nitric oxide protects b-cells against virally mediated lysis by limiting EMCV replication. This protection requires low micromolar, or iNOS derived, levels of nitric oxide. At these concentrations nitric oxide inhibits the Krebs enzyme aconitase and complex IV of the electron transport chain. Like nitric oxide, pharmacological inhibition of mitochondrial oxidative metabolism attenuates EMCV-mediated b-cell lysis by inhibiting viral replication. These findings provide novel evidence that cytokine signaling in b-cells functions to limit viral replication and subsequent b-cell lysis by attenuating mitochondrial oxidative metabolism in a nitric oxide–dependent manner.
Recommended Citation
J. D. Stafford et al., "Inhibition of mitochondrial oxidative metabolism attenuates EMCV replication and protects b-cells from virally mediated lysis," Journal of Biological Chemistry, vol. 295, no. 49, pp. 16655 - 16664, Elsevier, Sep 2020.
The definitive version is available at https://doi.org/doi.org/10.1074/jbc.RA120.014851
Department(s)
Biological Sciences
Publication Status
Open Access
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2023 The Authors, all rights reserved.
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution-Share Alike 4.0 License.
Publication Date
September 24, 2020
