Role of influenza A virus NP acetylation on viral growth and replication

Giese, Sebastian; Ciminski, Kevin; Bolte, Hardin; Moreira, Étori Aguiar; Lakdawala, Seema; Hu, Zehan; David, Quinnlan; Kolesnikova, Larissa; Götz, Veronika; Zhao, Yongxu; Dengjel, Jörn; Chin, Y. Eugene; Xu, Ke; Schwemmle, Martin

doi:10.1038/s41467-017-01112-3

Back

Journal article

+ 1 other files

Role of influenza A virus NP acetylation on viral growth and replication

Giese, Sebastian Institute of Virology, Medical Center University of Freiburg, Germany - Faculty of Medicine, University of Freiburg, Germany
Ciminski, Kevin Institute of Virology, Medical Center University of Freiburg, Germany - Faculty of Medicine, University of Freiburg, Germany
Bolte, Hardin Institute of Virology, Medical Center University of Freiburg, Germany - Faculty of Medicine, University of Freiburg, Germany - Spemann Graduate School of Biology and Medicine, University of Freiburg, Germany - Faculty of Biology, University of Freiburg, Germany
Moreira, Étori Aguiar Institute of Virology, Medical Center University of Freiburg, Germany - Faculty of Medicine, University of Freiburg, Germany - Spemann Graduate School of Biology and Medicine, University of Freiburg, Germany - Faculty of Biology, University of Freiburg, Germany - Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
Lakdawala, Seema Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, USA
Hu, Zehan Department of Dermatology, Medical Center, University of Freiburg, Germany - Department of Biology, University of Fribourg, Fribourg, Switzerland
David, Quinnlan Institute of Virology, Medical Center University of Freiburg, Germany - Faculty of Medicine, University of Freiburg, Germany
Kolesnikova, Larissa Institute of Virology, Philipps-Universität Marburg, Germany
Götz, Veronika Institute of Virology, Medical Center University of Freiburg, Germany - Faculty of Medicine, University of Freiburg, Germany
Zhao, Yongxu Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China
Dengjel, Jörn Department of Dermatology, Medical Center, University of Freiburg, Germany - Department of Biology, University of Fribourg, Fribourg, Switzerland
Chin, Y. Eugene Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai China
Xu, Ke Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Shanghai, China
Schwemmle, Martin Institute of Virology, Medical Center University of Freiburg, Germany - Faculty of Medicine, University of Freiburg, Germany

02.11.2017

Published in:

Nature Communications. - 2017, vol. 8, no. 1, p. 1259

English 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.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language