Dengue virus NS1 secretion is regulated via importin-subunit β1 controlling expression of the chaperone GRp78 and targeted by the clinical drug ivermectin

• DOI: 10.1128/mbio.01441-23
• Publication Date: 2023-09-13T13:00:35Z
• Authors: Solène Denolly; Hongbo Guo; Miriam Martens; Anna Płaszczyca; Pietro Scaturro; Vibhu Prasad; Kessiri Kongmanas; Nuntaya Punyadee; Adisak Songjaeng; Dumrong Mairiang; Andreas Pichlmair; Panisadee Avirutnan; Ralf Bartenschlager
• Keywords: Chaperone (clinical)

Dengue virus (DENV) is a major human pathogen that can cause hemorrhagic fever and shock syndrome. One important factor of DENV pathogenicity non-structural protein 1 (NS1), glycoprotein secreted from infected cells. Here we study the mode action widely used drug ivermectin, to treat parasitic infections recently shown lower NS1 blood levels in DENV-infected patients. We found ivermectin blocks nuclear transport transcription factors required for expression chaperones support folding secretion glycoproteins, including NS1. Impairing these by or depleting them cells dampens thus its secretion. These results reveal novel might apply other flaviviruses as well.