Novel role of bone morphogenetic protein 9 in innate host responses to HCMV infection.

Autor:	Stempel M; Institute of Genetics, Technische Universität Braunschweig, Braunschweig, Germany.; Virology and Innate Immunity Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany., Maier O; Institute of Genetics, Technische Universität Braunschweig, Braunschweig, Germany., Mhlekude B; Virology and Innate Immunity Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany., Drakesmith H; MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK., Brinkmann MM; Institute of Genetics, Technische Universität Braunschweig, Braunschweig, Germany. m.brinkmann@tu-braunschweig.de.; Virology and Innate Immunity Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany. m.brinkmann@tu-braunschweig.de.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Mar; Vol. 25 (3), pp. 1106-1129. Date of Electronic Publication: 2024 Mar 11.
DOI:	10.1038/s44319-024-00072-2
Abstrakt:	Herpesviruses modulate immune control to secure lifelong infection. The mechanisms Human Cytomegalovirus (HCMV) employs in this regard can reveal unanticipated aspects of cellular signaling involved in antiviral immunity. Here, we describe a novel relationship between the TGF-β family cytokine BMP9 and HCMV infection. We identify a cross-talk between BMP9-induced and IFN receptor-mediated signaling, showing that BMP9 boosts the transcriptional response to and antiviral activity of IFNβ, thereby enhancing viral restriction. We also show that BMP9 is secreted by human fibroblasts upon HCMV infection. However, HCMV infection impairs BMP9-induced enhancement of the IFNβ response, indicating that this signaling role of BMP9 is actively targeted by HCMV. Indeed, transmembrane proteins US18 and US20, which downregulate type I BMP receptors, are necessary and sufficient to cause inhibition of BMP9-mediated boosting of the antiviral response to IFNβ. HCMV lacking US18 and US20 is more sensitive to IFNβ. Thus, HCMV has a mutually antagonistic relationship with BMP9, which extends the growing body of evidence that BMP signaling is an underappreciated modulator of innate immunity in response to viral infection. (© 2024. The Author(s).)
Databáze:	MEDLINE
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