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Dengue virus NS1 secretion is regulated via importin-subunit ß1 controlling expression of the chaperone GRp78 and targeted by the clinical drug ivermectin.
Denolly, Solène; Guo, Hongbo; Martens, Miriam; Plaszczyca, Anna; Scaturro, Pietro; Prasad, Vibhu; Kongmanas, Kessiri; Punyadee, Nuntaya; Songjaeng, Adisak; Mairiang, Dumrong; Pichlmair, Andreas; Avirutnan, Panisadee; Bartenschlager, Ralf.
Afiliação
  • Denolly S; Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research, Heidelberg University, Medical Faculty Heidelberg , Heidelberg, Germany.
  • Guo H; Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research, Heidelberg University, Medical Faculty Heidelberg , Heidelberg, Germany.
  • Martens M; Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research, Heidelberg University, Medical Faculty Heidelberg , Heidelberg, Germany.
  • Plaszczyca A; Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research, Heidelberg University, Medical Faculty Heidelberg , Heidelberg, Germany.
  • Scaturro P; Technical University of Munich, School of Medicine, Institute of Virology , Munich, Germany.
  • Prasad V; Leibniz Institute of Virology , Hamburg, Germany.
  • Kongmanas K; Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research, Heidelberg University, Medical Faculty Heidelberg , Heidelberg, Germany.
  • Punyadee N; Division of Dengue Hemorrhagic Fever Research, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand.
  • Songjaeng A; Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand.
  • Mairiang D; Division of Dengue Hemorrhagic Fever Research, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand.
  • Pichlmair A; Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand.
  • Avirutnan P; Division of Dengue Hemorrhagic Fever Research, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand.
  • Bartenschlager R; Siriraj Center of Research Excellence in Dengue and Emerging Pathogens, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand.
mBio ; 14(5): e0144123, 2023 Oct 31.
Article em En | MEDLINE | ID: mdl-37702492
IMPORTANCE: Dengue virus (DENV) is a major human pathogen that can cause hemorrhagic fever and shock syndrome. One important factor of DENV pathogenicity is non-structural protein 1 (NS1), a glycoprotein that is secreted from infected cells. Here we study the mode of action of the widely used drug ivermectin, used to treat parasitic infections and recently shown to lower NS1 blood levels in DENV-infected patients. We found that ivermectin blocks the nuclear transport of transcription factors required for the expression of chaperones that support the folding and secretion of glycoproteins, including NS1. Impairing nuclear transport of these transcription factors by ivermectin or depleting them from infected cells dampens NS1 folding and thus its secretion. These results reveal a novel mode of action of ivermectin that might apply to other flaviviruses as well.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dengue / Vírus da Dengue Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dengue / Vírus da Dengue Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article