Resistance to ectromelia virus infection requires cGAS in bone marrow-derived cells which can be bypassed with cGAMP therapy

English version

Autoři: Eric B. Wong ^aff001; Brian Montoya ^aff001; Maria Ferez ^aff001; Colby Stotesbury ^aff001; Luis J. Sigal ^aff001
Působiště autorů: Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, Pennsylvania, United States of America ^aff001
Vyšlo v časopise: Resistance to ectromelia virus infection requires cGAS in bone marrow-derived cells which can be bypassed with cGAMP therapy. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008239
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008239

Souhrn

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.

Klíčová slova:

Cytokines – Chemokines – Interferons – NK cells – Skin infections – Spleen – Viral replication

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