Human cytomegalovirus blocks canonical TGF β signaling during lytic infection to limit induction of type I interferons

Andrew H. Pham, Jennifer Mitchell, Sara Botto, Kara M. Pryke, Victor De Filippis, Meaghan H. Hancock

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere1009380
JournalPLoS pathogens
Volume17
Issue number8
DOIs
StatePublished - Aug 2021

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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