The dynamic proteome of influenza A virus infection identifies M segment splicing as a host range determinant

Bogdanow, Boris1,2,7; Wang, Xi1,8; Eichelbaum, Katrin1; Sadewasser, Anne2; Husic, Immanuel1; Paki, Katharina2; Budt, Matthias2; Hergeselle, Martha1; Vetter, Barbara3; Hou, Jingyi1; Chen, Wei1,4; Wiebusch, Lueder3; Meyer, Irmtraud M.1,5; Wolff, Thorsten2; Selbach, Matthias1,6

2019-12-04

10.1038/s41467-019-13520-8

Nature Communications   影响因子和分区

2041-1723

Pandemic influenza A virus (IAV) outbreaks occur when strains from animal reservoirs acquire the ability to infect and spread among humans. The molecular basis of this species barrier is incompletely understood. Here we combine metabolic pulse labeling and quantitative proteomics to monitor protein synthesis upon infection of human cells with a human-and a bird-adapted IAV strain and observe striking differences in viral protein synthesis. Most importantly, the matrix protein M1 is inefficiently produced by the bird-adapted strain. We show that impaired production of M1 from bird-adapted strains is caused by increased splicing of the M segment RNA to alternative isoforms. Strain-specific M segment splicing is controlled by the 3' splice site and functionally important for permissive infection. In silico and biochemical evidence shows that avian-adapted M segments have evolved different conserved RNA structure features than human-adapted sequences. Thus, we identify M segment RNA splicing as a viral host range determinant.

SCI

英语

NI期刊

其他

German Ministry of Education and Research[0316180B]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000500506500001

NATURE PUBLISHING GROUP

Web of Science

1.Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13125 Berlin, Germany
2.Robert Koch Inst, Unit Influenza & Other Resp Viruses 17, Seestr 10, D-13353 Berlin, Germany
3.Charite Univ Med Berlin, Lab Padiatr Mol Biol, Augustenburger Pl 1, D-13353 Berlin, Germany
4.Southern Univ Sci & Technol, Dept Biol, Xuanyuan Rd 1088, Shenzhen 518055, Guangdong, Peoples R China
5.Free Univ Berlin, Dept Biol Chem Pharm, Inst Chem & Biochem, Thielallee 63, D-14195 Berlin, Germany
6.Charite Univ Med Berlin, D-10117 Berlin, Germany
7.Leibniz Forsch Inst Mol Pharmakol, Struct Interact, Robert Rossle Str 10, D-13125 Berlin, Germany
8.German Canc Res Ctr, Div Theoret Syst Biol, D-69120 Heidelberg, Germany

Bogdanow, Boris,Wang, Xi,Eichelbaum, Katrin,et al. The dynamic proteome of influenza A virus infection identifies M segment splicing as a host range determinant[J]. Nature Communications,2019,10.

Bogdanow, Boris.,Wang, Xi.,Eichelbaum, Katrin.,Sadewasser, Anne.,Husic, Immanuel.,...&Selbach, Matthias.(2019).The dynamic proteome of influenza A virus infection identifies M segment splicing as a host range determinant.Nature Communications,10.

Bogdanow, Boris,et al."The dynamic proteome of influenza A virus infection identifies M segment splicing as a host range determinant".Nature Communications 10(2019).