Editor(s)
Charles E. Samuel
Abstract
Viral infection is an environmental trigger that has been suggested to initiate pancreatic β-cell damage, leading to the development of autoimmune diabetes. Viruses potently activate the immune system and can damage β-cells by either directly infecting them or stimulating the production of secondary effector molecules (such as proinflammatory cytokines) during bystander activation. However, how and where β-cells recognize viruses is unclear, and the antiviral responses that are initiated following virus recognition are incompletely understood. In this study, we show that the β-cell response to dsRNA, a viral replication intermediate known to activate antiviral responses, is determined by the cellular location of sensing (intracellular versus extracellular) and differs from the cellular response to cytokine treatment. Using biochemical and immunological methods, we show that β -ells selectively respond to intracellular dsRNA by expressing type I interferons (IFNs) and inducing apoptosis, but that they do not respond to extracellular dsRNA. These responses differ from the activities of cytokines on β-cells, which are mediated by inducible nitric oxide synthase expression and β-cell production of nitric oxide. These findings provide evidence that the antiviral activities of type I IFN production and apoptosis are elicited in β-cells via the recognition of intracellular viral replication intermediates and that β-cells lack the capacity to respond to extracellular viral intermediates known to activate innate immune responses.
Recommended Citation
Z. R. Shaheen et al., "The location of sensing determines the pancreatic β-cell response to the viral mimetic dsRNA," Journal of Biological Chemistry, vol. 295, no. 8, pp. 2385 - 2397, Elsevier, Jan 2020.
The definitive version is available at https://doi.org/doi.org/10.1074/jbc.RA119.010267
Department(s)
Biological Sciences
Publication Status
Open Access
Document Type
Article - Journal
Document Version
Final Version
File Type
text
Language(s)
English
Rights
© 2025 The Authors, All rights reserved
Creative Commons Licensing
This work is licensed under a Creative Commons Attribution-Share Alike 4.0 License.
Publication Date
January 8, 2020
PubMed ID
31915247
