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

Boris Bogdanow, Xi Wang, Katrin Eichelbaum, Anne Sadewasser, Immanuel Husic, Katharina Paki, Matthias Budt, Martha Hergeselle, Barbara Vetter, Jingyi Hou, Wei Chen, Lüder Wiebusch, Irmtraud M. Meyer, Thorsten Wolff and Matthias Selbach ()
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Boris Bogdanow: Max Delbrück Center for Molecular Medicine
Xi Wang: Max Delbrück Center for Molecular Medicine
Katrin Eichelbaum: Max Delbrück Center for Molecular Medicine
Anne Sadewasser: Robert Koch Institut
Immanuel Husic: Max Delbrück Center for Molecular Medicine
Katharina Paki: Robert Koch Institut
Matthias Budt: Robert Koch Institut
Martha Hergeselle: Max Delbrück Center for Molecular Medicine
Barbara Vetter: Charité Universitätsmedizin Berlin
Jingyi Hou: Max Delbrück Center for Molecular Medicine
Wei Chen: Max Delbrück Center for Molecular Medicine
Lüder Wiebusch: Charité Universitätsmedizin Berlin
Irmtraud M. Meyer: Max Delbrück Center for Molecular Medicine
Thorsten Wolff: Robert Koch Institut
Matthias Selbach: Max Delbrück Center for Molecular Medicine

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-13520-8

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