Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons.

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-stimul...

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Autores principales:	Andrew H Pham, Jennifer Mitchell, Sara Botto, Kara M Pryke, Victor R DeFilippis, Meaghan H Hancock
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f33fe872ec0342febd4b8131762b77cc
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spelling	oai:doaj.org-article:f33fe872ec0342febd4b8131762b77cc2021-12-02T20:00:23ZHuman cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons.1553-73661553-737410.1371/journal.ppat.1009380https://doaj.org/article/f33fe872ec0342febd4b8131762b77cc2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009380https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Human 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.Andrew H PhamJennifer MitchellSara BottoKara M PrykeVictor R DeFilippisMeaghan H HancockPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 8, p e1009380 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Andrew H Pham Jennifer Mitchell Sara Botto Kara M Pryke Victor R DeFilippis Meaghan H Hancock Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons.
description	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.
format	article
author	Andrew H Pham Jennifer Mitchell Sara Botto Kara M Pryke Victor R DeFilippis Meaghan H Hancock
author_facet	Andrew H Pham Jennifer Mitchell Sara Botto Kara M Pryke Victor R DeFilippis Meaghan H Hancock
author_sort	Andrew H Pham
title	Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons.
title_short	Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons.
title_full	Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons.
title_fullStr	Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons.
title_full_unstemmed	Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons.
title_sort	human cytomegalovirus blocks canonical tgfβ signaling during lytic infection to limit induction of type i interferons.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/f33fe872ec0342febd4b8131762b77cc
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Human cytomegalovirus blocks canonical TGFβ signaling during lytic infection to limit induction of type I interferons.

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