Modified Vaccinia Virus Ankara Triggers Type I IFN Production in Murine Conventional Dendritic Cells via a cGAS/STING-Mediated Cytosolic DNA-Sensing Pathway

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Modified vaccinia virus Ankara (MVA) is an attenuated vaccinia strain with large deletions of the parental genome that render it non-replicative in mammalian cells. MVA is a safe and effective vaccine against both smallpox and monkeypox. MVA has been investigated as a vaccine vector for infectious diseases and cancers. Dendritic cells (DCs) play important roles in innate and adaptive immunity. A better understanding of how MVA is detected by innate immune sensors in DCs would guide the development of more effective MVA-based vaccines. We report our findings that MVA infection induces the production of type I interferon (IFN) in conventional dendritic cells via a cytosolic DNA-sensing pathway mediated by the newly discovered DNA sensor cGAS, its adaptor STING, and transcription factors IRF3 and IRF7. By contrast, wild-type vaccinia virus fails to activate this pathway. Furthermore, we show that vaccinia virulence factors E3 and N1 play inhibitory roles in the cytosolic DNA-sensing pathway.

Vyšlo v časopise: Modified Vaccinia Virus Ankara Triggers Type I IFN Production in Murine Conventional Dendritic Cells via a cGAS/STING-Mediated Cytosolic DNA-Sensing Pathway. PLoS Pathog 10(4): e32767. doi:10.1371/journal.ppat.1003989
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003989

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