Effects of mutations in the effector domain of influenza A virus NS1 protein

Pereira, C.F., Wise, H.M., Kurian, D., Pinto, R.M., Amorim, M.J., Gill, A.C. ORCID: 0000-0001-5201-9473 and Digard, P., 2018. Effects of mutations in the effector domain of influenza A virus NS1 protein. BMC Research Notes, 11: 673. ISSN 1756-0500

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Abstract

Objective: The multifunctional NS1 protein of influenza A virus has roles in antagonising cellular innate immune responses and promoting viral gene expression. To better understand the interplay between these functions, we tested the effects of NS1 effector domain mutations known to affect homo-dimerisation or interactions with cellular PI3 kinase or Trim25 on NS1 ability to promote nuclear export of viral mRNAs.

Results: The NS1 dimerisation mutant W187R retained the functions of binding cellular NXF1 as well as stabilising NXF1 interaction with viral segment 7 mRNAs and promoting their nuclear export. Two PI3K-binding mutants, NS1 Y89F and Y89A still bound NXF1 but no longer promoted NXF1 interactions with segment 7 mRNA or its nuclear export. The Trim25-binding mutant NS1 E96A/E97A bound NXF1 and supported NXF1 interactions with segment 7 mRNA but no longer supported mRNA nuclear export. Analysis of WT and mutant NS1 interaction partners identified hsp70 as specifically binding to NS1 E96A/E97A. Whilst these data suggest the possibility of functional links between NS1’s effects on intracellular signalling and its role in viral mRNA nuclear export, they also indicate potential pleiotropic effects of the NS1 mutations; in the case of E96A/E97A possibly via disrupted protein folding leading to chaperone recruitment.

Item Type: Journal article
Publication Title: BMC Research Notes
Creators: Pereira, C.F., Wise, H.M., Kurian, D., Pinto, R.M., Amorim, M.J., Gill, A.C. and Digard, P.
Publisher: BioMed Central
Date: 2018
Volume: 11
ISSN: 1756-0500
Identifiers:
NumberType
10.1186/s13104-018-3779-6DOI
2192527Other
Rights: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Divisions: Schools > School of Animal, Rural and Environmental Sciences
Record created by: Jonathan Gallacher
Date Added: 14 Aug 2024 07:47
Last Modified: 14 Aug 2024 07:47
URI: https://irep.ntu.ac.uk/id/eprint/51995

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