Document Type
Article
Publication Date
12-26-2019
Abstract
Cells sensing infection produce Type I interferons (IFN-I) to stimulate Interferon Stimulated Genes (ISGs) that confer resistance to viruses. During lympho-hematogenous spread of the mouse pathogen ectromelia virus (ECTV), the adaptor STING and the transcription factor IRF7 are required for IFN-I and ISG induction and resistance to ECTV. However, it is unknown which cells sense ECTV and which pathogen recognition receptor (PRR) upstream of STING is required for IFN-I and ISG induction. We found that cyclic-GMP-AMP (cGAMP) synthase (cGAS), a DNA-sensing PRR, is required in bone marrow-derived (BMD) but not in other cells for IFN-I and ISG induction and for resistance to lethal mousepox. Also, local administration of cGAMP, the product of cGAS that activates STING, rescues cGAS but not IRF7 or IFN-I receptor deficient mice from mousepox. Thus, sensing of infection by BMD cells via cGAS and IRF7 is critical for resistance to a lethal viral disease in a natural host.
Recommended Citation
Wong, Eric B.; Montoya, Brian; Ferez, Maria; Stotesbury, Colby; and Sigal, Luis J., "Resistance to ectromelia virus infection requires cGAS in bone marrow-derived cells which can be bypassed with cGAMP therapy." (2019). Department of Microbiology and Immunology Faculty Papers. Paper 113.
https://jdc.jefferson.edu/mifp/113
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
31877196
Language
English
Comments
This article is the author’s final published version in PLoS Pathogens, Volume 15, Issue 12, December 2019, Article number e1008239.
The published version is available at https://doi.org/10.1371/journal.ppat.1008239. Copyright © Wong et al.
Publication made possible in part by support from the Thomas Jefferson University + Philadelphia University Open Access Fund