Abstract

Lysine acetylation is a post-translational modification known to regulate protein functions. Here we identify several acetylation sites of the influenza A virus nucleoprotein (NP), including the lysine residues K77, K113 and K229. Viral growth of mutant virus encoding K229R, mimicking a non-acetylated NP lysine residue, is severely impaired compared to wildtype or the mutant viruses encoding K77R or K113R. This attenuation is not the result of decreased polymerase activity, altered protein expression or disordered vRNP co-segregation but rather caused by impaired particle release. Interestingly, release deficiency is also observed mimicking constant acetylation at this site (K229Q), whereas virus encoding NP-K113Q could not be generated. However, mimicking NP hyper-acetylation at K77 and K229 severely diminishes viral polymerase activity, while mimicking NP hypo-acetylation at these sites has no effect on viral replication. These results suggest that NP acetylation at K77, K113 and K229 impacts multiple steps in viral replication of influenza A viruses.

Details

Title
Role of influenza A virus NP acetylation on viral growth and replication
Author
Giese, Sebastian 1 ; Ciminski, Kevin 1 ; Bolte, Hardin 2 ; Étori Aguiar Moreira 3 ; Lakdawala, Seema 4 ; Hu, Zehan 5 ; Quinnlan, David 1 ; Kolesnikova, Larissa 6 ; Götz, Veronika 1 ; Zhao, Yongxu 7 ; Dengjel, Jörn 5 ; Chin, Y Eugene 7 ; Xu, Ke 8 ; Schwemmle, Martin 1 

 Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany 
 Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Spemann Graduate School of Biology and Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany 
 Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Spemann Graduate School of Biology and Medicine, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland 
 Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA 
 Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany; Department of Biology, University of Fribourg, Fribourg, Switzerland 
 Institute of Virology, Philipps-Universität Marburg, Marburg, Germany 
 Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China 
 Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China 
Pages
1-11
Publication year
2017
Publication date
Nov 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2127937151
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.