Journal article
Determinants of Zika virus host tropism uncovered by deep mutational scanning
YX Setoh, AA Amarilla, NYG Peng, RE Griffiths, J Carrera, ME Freney, E Nakayama, S Ogawa, D Watterson, N Modhiran, FE Nanyonga, FJ Torres, A Slonchak, P Periasamy, NA Prow, B Tang, J Harrison, J Hobson-Peters, T Cuddihy, J Cooper-White Show all
Nature Microbiology | NATURE PUBLISHING GROUP | Published : 2019
Abstract
Arboviruses cycle between, and replicate in, both invertebrate and vertebrate hosts, which for Zika virus (ZIKV) involves Aedes mosquitoes and primates1. The viral determinants required for replication in such obligate hosts are under strong purifying selection during natural virus evolution, making it challenging to resolve which determinants are optimal for viral fitness in each host. Herein we describe a deep mutational scanning (DMS) strategy2–5 whereby a viral cDNA library was constructed containing all codon substitutions in the C-terminal 204 amino acids of ZIKV envelope protein (E). The cDNA library was transfected into C6/36 (Aedes) and Vero (primate) cells, with subsequent deep seq..
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Awarded by Daiichi Sankyo Foundation of Life Science
Funding Acknowledgements
This work was supported by the National Health and Medical Research Council (NHMRC) of Australia (grant No. APP1144950). A.K. and A.S. are Research Fellows with the NHMRC. E.N. was supported in part by the Daiichi Sankyo Foundation of Life Science, Japan. We thank R. Sullivan from the Queensland Brain Institute Microscopy and Histology Facility for help with preparation and imaging of the brain organoid slides. Organoid confocal microscopy work was performed in part at the Queensland node of the Australian National Fabrication Facility, a company established under the National Collaborative Research Infrastructure Strategy to provide nano-and microfabrication facilities for Australia's researchers.