Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons
Abstrak
Human cytomegalovirus (HCMV) microRNAs (miRNAs) significantly rewire host signaling pathways to support the viral lifecycle and regulate host cell responses. Here we show that SMAD3 expression is regulated by HCMV miR-UL22A and contributes to the IRF7-mediated induction of type I IFNs and IFN-stimulated genes (ISGs) in human fibroblasts. Addition of exogenous TGFβ interferes with the replication of a miR-UL22A mutant virus in a SMAD3-dependent manner in wild type fibroblasts, but not in cells lacking IRF7, indicating that downregulation of SMAD3 expression to limit IFN induction is important for efficient lytic replication. These findings uncover a novel interplay between SMAD3 and innate immunity during HCMV infection and highlight the role of viral miRNAs in modulating these responses.
Penulis (6)
Andrew H. Pham
Jennifer Mitchell
Sara Botto
Kara M. Pryke
Victor R. DeFilippis
Meaghan H. Hancock
Akses Cepat
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- 2021
- Bahasa
- en
- Total Sitasi
- 9×
- Sumber Database
- CrossRef
- DOI
- 10.1371/journal.ppat.1009380
- Akses
- Open Access ✓