A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors | Zendy

Mohamed Lamine Hafirassou | Zendy; Laurent Meertens | Zendy; Claudia Umaña-Diaz | Zendy; Athéna Labeau | Zendy; Ophélie Dejarnac | Zendy; Lucie BonnetMadin | Zendy; Beate M. Kümmerer | Zendy; Constance Delaugerre | Zendy; Philippe Roingeard | Zendy; PierreOlivier Vidalain | Zendy; Ali Amara | Zendy

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A Global Interactome Map of the Dengue Virus NS1 Identifies Virus Restriction and Dependency Host Factors

Author(s) -

Mohamed Lamine Hafirassou,

Laurent Meertens,

Claudia Umaña-Diaz,

Athéna Labeau,

Ophélie Dejarnac,

Lucie BonnetMadin,

Beate M. Kümmerer,

Constance Delaugerre,

Philippe Roingeard,

PierreOlivier Vidalain,

Ali Amara

Publication year - 2017

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2017.11.094

Subject(s) - interactome , dengue virus , biology , dengue fever , virology , viral replication , host (biology) , glycosylation , virus , computational biology , rna interference , genetics , gene , rna

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.

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