Entry by multiple picornaviruses is dependent on a pathway that includes TNK2, WASL and NCK1
- Washington University in St Louis, United States
Abstract
Comprehensive knowledge of the host factors required for picornavirus infection would facilitate antiviral development. Here we demonstrate roles for three human genes, TNK2, WASL, and NCK1, in infection by multiple picornaviruses. CRISPR deletion of TNK2, WASL or NCK1 reduced encephalomyocarditis virus (EMCV), coxsackievirus B3 (CVB3), poliovirus and enterovirus D68 infection, and chemical inhibitors of TNK2 and WASL decreased EMCV infection. Reduced EMCV lethality was observed in mice lacking TNK2. TNK2, WASL and NCK1 were important in early stages of the viral lifecycle, and genetic epistasis analysis demonstrated that the three genes function in a common pathway. Mechanistically, reduced internalization of EMCV was observed in TNK2 deficient cells demonstrating that TNK2 functions in EMCV entry. Domain analysis of WASL demonstrated that its actin nucleation activity was necessary to facilitate viral infection. Together, these data support a model wherein TNK2, WASL, and NCK1 comprise a pathway important for multiple picornaviruses.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files were provided.
Article and author information
Author details
Funding
National Institutes of Health (R01 AI134967)
- David Wang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experiments were conducted under the supervision of Department of Comparative Medicine at Washington University in St. Louis. All animal protocols were approved by the Washington University Institutional Animal Care and Use Committee (Protocol #20170194 and #20180289).
Copyright
© 2019, Jiang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Entry by multiple picornaviruses is dependent on a pathway that includes TNK2, WASL and NCK1
eLife 8:e50276.
https://doi.org/10.7554/eLife.50276
