Document Type
Article
Publication Date
1-24-2025
Abstract
Although viruses subvert innate immune pathways for their replication, there is evidence they can also co-opt antiviral responses for their benefit. The ubiquitous human pathogen, Herpes simplex virus-1 (HSV-1), encodes a protein (UL12.5) that induces the release of mitochondrial nucleic acid into the cytosol, which activates immune-sensing pathways and reduces productive replication in nonneuronal cells. HSV-1 establishes latency in neurons and can reactivate to cause disease. We found that UL12.5 is required for HSV-1 reactivation in neurons and acts to directly promote viral lytic gene expression during initial exit from latency. Further, the direct activation of innate immune-sensing pathways triggered HSV-1 reactivation and compensated for a lack of UL12.5. Finally, we found that the induction of HSV-1 lytic genes during reactivation required intact RNA- and DNA-sensing pathways, demonstrating that HSV-1 can respond to and active antiviral nucleic acid-sensing pathways to reactivate from a latent infection.
Recommended Citation
Krakowiak, Patryk A.; Flores, Matthew E.; Cuddy, Sean R.; Whitford, Abigail L.; Dochnal, Sara A.; Babnis, Aleksandra; Miyake, Tsuyoshi; Tigano, Marco; Engel, Daniel A.; and Cliffe, Anna R., "Co-option of Mitochondrial Nucleic Acid-Sensing Pathways by HSV-1 UL12.5 for Reactivation From Latent Infection" (2025). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 435.
https://jdc.jefferson.edu/pacbfp/435
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
39854226
Language
English
Comments
This article is the author's final published version in Proceedings of the National Academy of Sciences of the United States of America, Volume 122, Issue 4, January 2025, Article number e2413965122.
The published version is available at https://doi.org/10.1073/pnas.2413965122.
Copyright © 2025 The Author(s).