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Viruses 2016, 8(10), 287;

4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression

Department of Immunology and Microbiology, University of Colorado Graduate School, Aurora, CO 80045, USA
Department of Medicine, Division of Infectious Diseases, University of Colorado School of Medicine, Aurora, CO 80045, USA
Author to whom correspondence should be addressed.
Academic Editor: Michael R. Holbrook
Received: 8 July 2016 / Revised: 16 September 2016 / Accepted: 7 October 2016 / Published: 18 October 2016
(This article belongs to the Special Issue Advances in Flavivirus Research)
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West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an m7GpppNm 5′ cap with 2′-O-methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1) for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown. In this study, we utilize gene deletion mutants in the ribosomal protein kinase called S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein (4EBP) pathways downstream of mTORC1 to define the role of mTOR-dependent translation initiation signals in WNV gene expression and growth. We now show that WNV growth and protein expression are dependent on mTORC1 mediated-regulation of the eukaryotic translation initiation factor 4E-binding protein/eukaryotic translation initiation factor 4E-binding protein (4EBP/eIF4E) interaction and eukaryotic initiation factor 4F (eIF4F) complex formation to support viral growth and viral protein expression. We also show that the canonical signals of mTORC1 activation including ribosomal protein s6 (rpS6) and S6K phosphorylation are not required for WNV growth in these same conditions. Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome. View Full-Text
Keywords: West Nile virus; RNA; translation; protein synthesis West Nile virus; RNA; translation; protein synthesis

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Shives, K.D.; Massey, A.R.; May, N.A.; Morrison, T.E.; Beckham, J.D. 4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression. Viruses 2016, 8, 287.

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