A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors
Mohamed Lamine Hafirassou,
Laurent Meertens,
Claudia Umaña-Diaz,
Athena Labeau,
Ophelie Dejarnac,
Lucie Bonnet-Madin,
Beate M. Kümmerer,
Constance Delaugerre,
Philippe Roingeard,
Pierre-Olivier Vidalain,
Ali Amara
Affiliations
Mohamed Lamine Hafirassou
INSERM U944, CNRS UMR 7212, Institut Universitaire d’Hématologie, Sorbonne Paris Cité, Université Paris Diderot, Hôpital Saint Louis, 75010 Paris, France
Laurent Meertens
INSERM U944, CNRS UMR 7212, Institut Universitaire d’Hématologie, Sorbonne Paris Cité, Université Paris Diderot, Hôpital Saint Louis, 75010 Paris, France
Claudia Umaña-Diaz
INSERM U944, CNRS UMR 7212, Institut Universitaire d’Hématologie, Sorbonne Paris Cité, Université Paris Diderot, Hôpital Saint Louis, 75010 Paris, France
Athena Labeau
INSERM U944, CNRS UMR 7212, Institut Universitaire d’Hématologie, Sorbonne Paris Cité, Université Paris Diderot, Hôpital Saint Louis, 75010 Paris, France
Ophelie Dejarnac
INSERM U944, CNRS UMR 7212, Institut Universitaire d’Hématologie, Sorbonne Paris Cité, Université Paris Diderot, Hôpital Saint Louis, 75010 Paris, France
Lucie Bonnet-Madin
INSERM U944, CNRS UMR 7212, Institut Universitaire d’Hématologie, Sorbonne Paris Cité, Université Paris Diderot, Hôpital Saint Louis, 75010 Paris, France
Beate M. Kümmerer
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
Constance Delaugerre
Departement des Maladies Infectieuses, Hôpital Saint Louis, 75010 Paris, France
Philippe Roingeard
INSERM U966 MAVIVH, Faculté de Médecine, Université de Tours, Tours, France
Pierre-Olivier Vidalain
Equipe Chimie & Biologie, Modélisation et Immunologie pour la Thérapie, Université Paris Descartes, CNRS UMR 8601, Paris, France
Ali Amara
INSERM U944, CNRS UMR 7212, Institut Universitaire d’Hématologie, Sorbonne Paris Cité, Université Paris Diderot, Hôpital Saint Louis, 75010 Paris, France
Dengue virus (DENV) infections cause the most prevalent mosquito-borne viral disease worldwide, for which no therapies are available. DENV encodes seven non-structural (NS) proteins that co-assemble and recruit poorly characterized host factors to form the DENV replication complex essential for viral infection. Here, we provide a global proteomic analysis of the human host factors that interact with the DENV NS1 protein. Combined with a functional RNAi screen, this study reveals a comprehensive network of host cellular processes involved in DENV infection and identifies DENV host restriction and dependency factors. We highlight an important role of RACK1 and the chaperonin TRiC (CCT) and oligosaccharyltransferase (OST) complexes during DENV replication. We further show that the OST complex mediates NS1 and NS4B glycosylation, and pharmacological inhibition of its N-glycosylation function strongly impairs DENV infection. In conclusion, our study provides a global interactome of the DENV NS1 and identifies host factors targetable for antiviral therapies.
