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Reciprocal Effects of Fibroblast Growth Factor Receptor Signaling on Dengue Virus Replication and Virion Production.
Cortese, Mirko; Kumar, Anil; Matula, Petr; Kaderali, Lars; Scaturro, Pietro; Erfle, Holger; Acosta, Eliana Gisela; Buehler, Sandra; Ruggieri, Alessia; Chatel-Chaix, Laurent; Rohr, Karl; Bartenschlager, Ralf.
Afiliação
  • Cortese M; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, Heidelberg 69120, Germany.
  • Kumar A; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, Heidelberg 69120, Germany.
  • Matula P; Biomedical Computer Vision Group, Heidelberg University, BioQuant, IPMB, and German Cancer Research Center, Im Neuenheimer Feld 267, Heidelberg 69120, Germany.
  • Kaderali L; ViroQuant Research Group Modeling, BioQuant, Heidelberg University, Heidelberg, Germany.
  • Scaturro P; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, Heidelberg 69120, Germany.
  • Erfle H; Advanced Biological Screening Facility, BioQuant, Heidelberg University, Heidelberg 69120, Germany.
  • Acosta EG; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, Heidelberg 69120, Germany.
  • Buehler S; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, Heidelberg 69120, Germany.
  • Ruggieri A; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, Heidelberg 69120, Germany.
  • Chatel-Chaix L; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, Heidelberg 69120, Germany; Institut National de la Recherche Scientifique, Institut Armand-Frappier, 531, Boulevard des Prairies Laval, Québec, QC H7V 1B7, Canada.
  • Rohr K; Biomedical Computer Vision Group, Heidelberg University, BioQuant, IPMB, and German Cancer Research Center, Im Neuenheimer Feld 267, Heidelberg 69120, Germany.
  • Bartenschlager R; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, Heidelberg 69120, Germany; German Center for Infection Research, Heidelberg Partner Site, Im Neuenheimer Feld 344, Heidelberg 69120, Germany. Electronic address: ralf.bartenschlager@med.uni-heidelb
Cell Rep ; 27(9): 2579-2592.e6, 2019 05 28.
Article em En | MEDLINE | ID: mdl-31141684
Dengue virus (DENV) is a human arboviral pathogen accounting for 390 million infections every year. The available vaccine has limited efficacy, and DENV-specific drugs have not been generated. To better understand DENV-host cell interaction, we employed RNA interference-based screening of the human kinome and identified fibroblast growth factor receptor 4 (FGFR4) to control the DENV replication cycle. Pharmacological inhibition of FGFR exerts a reciprocal effect by reducing DENV RNA replication and promoting the production of infectious virus particles. Addressing the latter effect, we found that the FGFR signaling pathway modulates intracellular distribution of DENV particles in a PI3K-dependent manner. Upon FGFR inhibition, virions accumulate in the trans-Golgi network compartment, where they undergo enhanced maturation cleavage of the envelope protein precursor membrane (prM), rendering virus particles more infectious. This study reveals an unexpected reciprocal role of a cellular receptor tyrosine kinase regulating DENV RNA replication and the production of infectious virions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírion / Replicação Viral / Proteínas não Estruturais Virais / Receptores de Fatores de Crescimento de Fibroblastos / Fosfatidilinositol 3-Quinases / Dengue / Vírus da Dengue Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírion / Replicação Viral / Proteínas não Estruturais Virais / Receptores de Fatores de Crescimento de Fibroblastos / Fosfatidilinositol 3-Quinases / Dengue / Vírus da Dengue Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article