Differential regulation of type I interferon and epidermal growth factor pathways by a human Respirovirus virulence factor.

A number of paramyxoviruses are responsible for acute respiratory infections in children, elderly and immuno-compromised individuals, resulting in airway inflammation and exacerbation of chronic diseases like asthma. To understand the molecular pathogenesis of these infections, we searched for cellu...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Grégory Caignard, Anastassia V Komarova, Mehdi Bouraï, Thomas Mourez, Yves Jacob, Louis M Jones, Flore Rozenberg, Astrid Vabret, François Freymuth, Frédéric Tangy, Pierre-Olivier Vidalain
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/71a79adf30ab4536b6204397d66ddeb5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:71a79adf30ab4536b6204397d66ddeb5
record_format	dspace
spelling	oai:doaj.org-article:71a79adf30ab4536b6204397d66ddeb52021-11-25T05:47:38ZDifferential regulation of type I interferon and epidermal growth factor pathways by a human Respirovirus virulence factor.1553-73661553-737410.1371/journal.ppat.1000587https://doaj.org/article/71a79adf30ab4536b6204397d66ddeb52009-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19806178/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374A number of paramyxoviruses are responsible for acute respiratory infections in children, elderly and immuno-compromised individuals, resulting in airway inflammation and exacerbation of chronic diseases like asthma. To understand the molecular pathogenesis of these infections, we searched for cellular targets of the virulence protein C of human parainfluenza virus type 3 (hPIV3-C). We found that hPIV3-C interacts directly through its C-terminal domain with STAT1 and GRB2, whereas C proteins from measles or Nipah viruses failed to do so. Binding to STAT1 explains the previously reported capacity of hPIV3-C to block type I interferon signaling, but the interaction with GRB2 was unexpected. This adaptor protein bridges Epidermal Growth Factor (EGF) receptor to MAPK/ERK pathway, a signaling cascade recently found to be involved in airway inflammatory response. We report that either hPIV3 infection or transient expression of hPIV3-C both increase cellular response to EGF, as assessed by Elk1 transactivation and phosphorylation levels of ERK1/2, 40S ribosomal subunit protein S6 and translation initiation factor 4E (eIF4E). Furthermore, inhibition of MAPK/ERK pathway with U0126 prevented viral protein expression in infected cells. Altogether, our data provide molecular basis to explain the role of hPIV3-C as a virulence factor and determinant of pathogenesis and demonstrate that Paramyxoviridae have evolved a single virulence factor to block type I interferon signaling and to boost simultaneous cellular response to growth factors.Grégory CaignardAnastassia V KomarovaMehdi BouraïThomas MourezYves JacobLouis M JonesFlore RozenbergAstrid VabretFrançois FreymuthFrédéric TangyPierre-Olivier VidalainPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 9, p e1000587 (2009)
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 Grégory Caignard Anastassia V Komarova Mehdi Bouraï Thomas Mourez Yves Jacob Louis M Jones Flore Rozenberg Astrid Vabret François Freymuth Frédéric Tangy Pierre-Olivier Vidalain Differential regulation of type I interferon and epidermal growth factor pathways by a human Respirovirus virulence factor.
description	A number of paramyxoviruses are responsible for acute respiratory infections in children, elderly and immuno-compromised individuals, resulting in airway inflammation and exacerbation of chronic diseases like asthma. To understand the molecular pathogenesis of these infections, we searched for cellular targets of the virulence protein C of human parainfluenza virus type 3 (hPIV3-C). We found that hPIV3-C interacts directly through its C-terminal domain with STAT1 and GRB2, whereas C proteins from measles or Nipah viruses failed to do so. Binding to STAT1 explains the previously reported capacity of hPIV3-C to block type I interferon signaling, but the interaction with GRB2 was unexpected. This adaptor protein bridges Epidermal Growth Factor (EGF) receptor to MAPK/ERK pathway, a signaling cascade recently found to be involved in airway inflammatory response. We report that either hPIV3 infection or transient expression of hPIV3-C both increase cellular response to EGF, as assessed by Elk1 transactivation and phosphorylation levels of ERK1/2, 40S ribosomal subunit protein S6 and translation initiation factor 4E (eIF4E). Furthermore, inhibition of MAPK/ERK pathway with U0126 prevented viral protein expression in infected cells. Altogether, our data provide molecular basis to explain the role of hPIV3-C as a virulence factor and determinant of pathogenesis and demonstrate that Paramyxoviridae have evolved a single virulence factor to block type I interferon signaling and to boost simultaneous cellular response to growth factors.
format	article
author	Grégory Caignard Anastassia V Komarova Mehdi Bouraï Thomas Mourez Yves Jacob Louis M Jones Flore Rozenberg Astrid Vabret François Freymuth Frédéric Tangy Pierre-Olivier Vidalain
author_facet	Grégory Caignard Anastassia V Komarova Mehdi Bouraï Thomas Mourez Yves Jacob Louis M Jones Flore Rozenberg Astrid Vabret François Freymuth Frédéric Tangy Pierre-Olivier Vidalain
author_sort	Grégory Caignard
title	Differential regulation of type I interferon and epidermal growth factor pathways by a human Respirovirus virulence factor.
title_short	Differential regulation of type I interferon and epidermal growth factor pathways by a human Respirovirus virulence factor.
title_full	Differential regulation of type I interferon and epidermal growth factor pathways by a human Respirovirus virulence factor.
title_fullStr	Differential regulation of type I interferon and epidermal growth factor pathways by a human Respirovirus virulence factor.
title_full_unstemmed	Differential regulation of type I interferon and epidermal growth factor pathways by a human Respirovirus virulence factor.
title_sort	differential regulation of type i interferon and epidermal growth factor pathways by a human respirovirus virulence factor.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/71a79adf30ab4536b6204397d66ddeb5
work_keys_str_mv	AT gregorycaignard differentialregulationoftypeiinterferonandepidermalgrowthfactorpathwaysbyahumanrespirovirusvirulencefactor AT anastassiavkomarova differentialregulationoftypeiinterferonandepidermalgrowthfactorpathwaysbyahumanrespirovirusvirulencefactor AT mehdibourai differentialregulationoftypeiinterferonandepidermalgrowthfactorpathwaysbyahumanrespirovirusvirulencefactor AT thomasmourez differentialregulationoftypeiinterferonandepidermalgrowthfactorpathwaysbyahumanrespirovirusvirulencefactor AT yvesjacob differentialregulationoftypeiinterferonandepidermalgrowthfactorpathwaysbyahumanrespirovirusvirulencefactor AT louismjones differentialregulationoftypeiinterferonandepidermalgrowthfactorpathwaysbyahumanrespirovirusvirulencefactor AT florerozenberg differentialregulationoftypeiinterferonandepidermalgrowthfactorpathwaysbyahumanrespirovirusvirulencefactor AT astridvabret differentialregulationoftypeiinterferonandepidermalgrowthfactorpathwaysbyahumanrespirovirusvirulencefactor AT francoisfreymuth differentialregulationoftypeiinterferonandepidermalgrowthfactorpathwaysbyahumanrespirovirusvirulencefactor AT frederictangy differentialregulationoftypeiinterferonandepidermalgrowthfactorpathwaysbyahumanrespirovirusvirulencefactor AT pierreoliviervidalain differentialregulationoftypeiinterferonandepidermalgrowthfactorpathwaysbyahumanrespirovirusvirulencefactor
_version_	1718414462567841792

Differential regulation of type I interferon and epidermal growth factor pathways by a human Respirovirus virulence factor.

Ejemplares similares