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

Boris Bogdanow, Katrin Eichelbaum, Anne Sadewasser, Xi Wang, Immanuel Husic, Katharina Paki, Martha Hergeselle, Barbara Vetter, Jingyi Hou, Wei Chen, Lüder Wiebusch, Irmtraud M. Meyer, Thorsten Wolff and Matthias Selbach

Go to the profile of Nature Communications
Nov 19, 2018
0
0

Received Date: 8th October 18

A century ago, influenza A virus (IAV) infection caused the 1918 flu pandemic and killed an estimated 20-40 million people. Pandemic IAV outbreaks occur when strains from animal reservoirs acquire the ability to infect and spread among humans. The molecular details of this species barrier are incompletely understood. We combined metabolic pulse labeling and quantitative shotgun proteomics to globally monitor protein synthesis upon infection of human cells with a human- and a bird-adapted IAV strain. While production of host proteins was remarkably similar, we observed striking differences in the kinetics of viral protein synthesis over the course of infection. Most importantly, the matrix protein M1 was inefficiently produced by the bird-adapted strain at later stages. We show that impaired production of M1 from bird-adapted strains is caused by increased splicing of the M segment RNA to alternative isoforms. Experiments with reporter constructs and recombinant influenza viruses revealed that strain-specific M segment splicing is controlled by the 3’ splice site and functionally important for permissive infection. Independent in silico evidence shows that avian-adapted M segments have evolved different conserved RNA structure features than human-adapted sequences. Thus, our data identifies M segment RNA splicing as a viral determinant of host range.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.


Go to the profile of Nature Communications

Nature Communications

Nature Research, Springer Nature