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

Cell Rep. 2017 Dec 26;21(13):3900-3913. doi: 10.1016/j.celrep.2017.11.094.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dengue / virology
  • Dengue Virus / metabolism*
  • Glycosylation
  • HEK293 Cells
  • HeLa Cells
  • Host-Pathogen Interactions*
  • Humans
  • Multiprotein Complexes / metabolism
  • Neoplasm Proteins / metabolism
  • Protein Interaction Maps*
  • RNA, Small Interfering / metabolism
  • Receptors for Activated C Kinase / metabolism
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication

Substances

  • Multiprotein Complexes
  • Neoplasm Proteins
  • RACK1 protein, human
  • RNA, Small Interfering
  • Receptors for Activated C Kinase
  • Viral Nonstructural Proteins