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Human genome-wide RNAi screen reveals host factors required for enterovirus 71 replication

Author

Listed:
  • Kan Xing Wu

    (National University of Singapore)

  • Patchara Phuektes

    (National University of Singapore)

  • Pankaj Kumar

    (Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR))

  • Germaine Yen Lin Goh

    (Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR))

  • Dimitri Moreau

    (Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR))

  • Vincent Tak Kwong Chow

    (National University of Singapore)

  • Frederic Bard

    (Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR))

  • Justin Jang Hann Chu

    (National University of Singapore
    Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR))

Abstract

Enterovirus 71 (EV71) is a neurotropic enterovirus without antivirals or vaccine, and its host-pathogen interactions remain poorly understood. Here we use a human genome-wide RNAi screen to identify 256 host factors involved in EV71 replication in human rhabdomyosarcoma cells. Enrichment analyses reveal overrepresentation in processes like mitotic cell cycle and transcriptional regulation. We have carried out orthogonal experiments to characterize the roles of selected factors involved in cell cycle regulation and endoplasmatic reticulum-associated degradation. We demonstrate nuclear egress of CDK6 in EV71 infected cells, and identify CDK6 and AURKB as resistance factors. NGLY1, which co-localizes with EV71 replication complexes at the endoplasmatic reticulum, supports EV71 replication. We confirm importance of these factors for EV71 replication in a human neuronal cell line and for coxsackievirus A16 infection. A small molecule inhibitor of NGLY1 reduces EV71 replication. This study provides a comprehensive map of EV71 host factors and reveals potential antiviral targets.

Suggested Citation

  • Kan Xing Wu & Patchara Phuektes & Pankaj Kumar & Germaine Yen Lin Goh & Dimitri Moreau & Vincent Tak Kwong Chow & Frederic Bard & Justin Jang Hann Chu, 2016. "Human genome-wide RNAi screen reveals host factors required for enterovirus 71 replication," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13150
    DOI: 10.1038/ncomms13150
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