Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms of Dengue and Zika Virus Pathogenesis | Zendy

Priya S. Shah | Zendy; Nichole Link | Zendy; Gwendolyn Μ. Jang | Zendy; Phillip P. Sharp | Zendy; Tongtong Zhu | Zendy; Danielle L. Swaney | Zendy; Jeffrey R. Johnson | Zendy; John Von Dollen | Zendy; Holly Ramage | Zendy; Laura Satkamp | Zendy; Billy W. Newton | Zendy; Ruth Hüttenhain | Zendy; Marine J. Petit | Zendy; Tierney Baum | Zendy; Amanda Everitt | Zendy; Orly Laufman | Zendy; Michel Tassetto | Zendy; Michael Shales | Zendy; Erica Stevenson | Zendy; Gabriel N. Iglesias | Zendy; L. Shokat | Zendy; Shashank Tripathi | Zendy; Vinod Balasubramaniam | Zendy; Laurence G. Webb | Zendy; Sebastián Aguirre | Zendy; A. Jeremy Willsey | Zendy; Adolfo Garcı́a-Sastre | Zendy; Katherine S. Pollard | Zendy; Sara Cherry | Zendy; Andrea V. Gamarnik | Zendy; Ivan Marazzi | Zendy; Jack Taunton | Zendy; Ana FernandezSesma | Zendy; Hugo J. Bellen | Zendy; Raul Andino | Zendy; Nevan J. Krogan | Zendy

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Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms of Dengue and Zika Virus Pathogenesis

Author(s) -

Priya S. Shah,

Nichole Link,

Gwendolyn Μ. Jang,

Phillip P. Sharp,

Tongtong Zhu,

Danielle L. Swaney,

Jeffrey R. Johnson,

John Von Dollen,

Holly Ramage,

Laura Satkamp,

Billy W. Newton,

Ruth Hüttenhain,

Marine J. Petit,

Tierney Baum,

Amanda Everitt,

Orly Laufman,

Michel Tassetto,

Michael Shales,

Erica Stevenson,

Gabriel N. Iglesias,

L. Shokat,

Shashank Tripathi,

Vinod Balasubramaniam,

Laurence G. Webb,

Sebastián Aguirre,

A. Jeremy Willsey,

Adolfo Garcı́a-Sastre,

Katherine S. Pollard,

Sara Cherry,

Andrea V. Gamarnik,

Ivan Marazzi,

Jack Taunton,

Ana FernandezSesma,

Hugo J. Bellen,

Raul Andino,

Nevan J. Krogan

Publication year - 2018

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2018.11.028

Subject(s) - zika virus , flavivirus , biology , dengue fever , dengue virus , virology , flaviviridae , viral replication , virus , microcephaly , vector (molecular biology) , gene , genetics , viral disease , recombinant dna

Mosquito-borne flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), are a growing public health concern. Systems-level analysis of how flaviviruses hijack cellular processes through virus-host protein-protein interactions (PPIs) provides information about their replication and pathogenic mechanisms. We used affinity purification-mass spectrometry (AP-MS) to compare flavivirus-host interactions for two viruses (DENV and ZIKV) in two hosts (human and mosquito). Conserved virus-host PPIs revealed that the flavivirus NS5 protein suppresses interferon stimulated genes by inhibiting recruitment of the transcription complex PAF1C and that chemical modulation of SEC61 inhibits DENV and ZIKV replication in human and mosquito cells. Finally, we identified a ZIKV-specific interaction between NS4A and ANKLE2, a gene linked to hereditary microcephaly, and showed that ZIKV NS4A causes microcephaly in Drosophila in an ANKLE2-dependent manner. Thus, comparative flavivirus-host PPI mapping provides biological insights and, when coupled with in vivo models, can be used to unravel pathogenic mechanisms.

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