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

被引：55

作者：

Giese, Sebastian ^{[1
,2
]}

Ciminski, Kevin ^{[1
,2
]}

Bolte, Hardin ^{[1
,2
,3
,4
]}

Moreira, Etori Aguiar ^{[1
,2
,3
,4
,11
]}

Lakdawala, Seema ^{[5
]}

Hu, Zehan ^{[6
,7
]}

David, Quinnlan ^{[1
,2
]}

Kolesnikova, Larissa ^{[8
]}

Goetz, Veronika ^{[1
,2
]}

Zhao, Yongxu ^{[9
]}

Dengjel, Joern ^{[6
,7
]}

Chin, Y. Eugene ^{[9
]}

Xu, Ke ^{[10
]}

Schwemmle, Martin ^{[1
,2
]}

机构：

[1] Univ Freiburg, Inst Virol, Med Ctr, D-79104 Freiburg, Germany

[2] Univ Freiburg, Fac Med, D-79104 Freiburg, Germany

[3] Univ Freiburg, Spemann Grad Sch Biol & Med, D-79104 Freiburg, Germany

[4] Univ Freiburg, Fac Biol, D-79104 Freiburg, Germany

[5] Univ Pittsburgh, Dept Microbiol & Mol Genet, Sch Med, Pittsburgh, PA 15217 USA

[6] Univ Freiburg, Dept Dermatol, Med Ctr, D-79110 Freiburg, Germany

[7] Univ Fribourg, Dept Biol, CH-79110 Fribourg, Switzerland

[8] Philipps Univ Marburg, Inst Virol, D-35043 Marburg, Germany

[9] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Shanghai 200031, Peoples R China

[10] Chinese Acad Sci, Inst Pasteur Shanghai, Shanghai Inst Biol Sci, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China

[11] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

ANTIVIRAL DRUG DEVELOPMENT; NUCLEAR EXPORT PROTEIN; CRYSTAL-STRUCTURE; RNA-BINDING; HISTONE H3; NUCLEOPROTEIN; RIBONUCLEOPROTEINS; PHOSPHORYLATION; UBIQUITINATION; CHROMOSOME;

D O I：

10.1038/s41467-017-01112-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 43 条

[1] Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2) [J].