Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs

Cédric Diot; Guillaume Fournier; Mélanie Dos Santos; Julie Magnus; Anastasia Komarova; Sylvie van der Werf; Sandie Munier; Nadia Naffakh

doi:10.1038/srep33763

Influenza A Virus Polymerase Recruits the RNA Helicase DDX19 to Promote the Nuclear Export of Viral mRNAs

Sci Rep. 2016 Sep 22:6:33763. doi: 10.1038/srep33763.

Authors

Cédric Diot^{1

2

3}, Guillaume Fournier^{1

2

3}, Mélanie Dos Santos^{1

2

3}, Julie Magnus^{1

2

3}, Anastasia Komarova^{2

4}, Sylvie van der Werf^{1

2

3}, Sandie Munier^{1

2

3}, Nadia Naffakh^{1

2

3}

Affiliations

¹ Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN, Département de Virologie, F-75015 Paris, France.
² CNRS, UMR3569, F-75015 Paris, France.
³ Université Paris Diderot, Sorbonne Paris Cité, Unité de Génétique Moléculaire des Virus à ARN, EA302, F-75015 Paris, France.
⁴ Institut Pasteur, Unité de Génomique Virale et Vaccination, Département de Virologie, F-75015 Paris, France.

Abstract

Enhancing the knowledge of host factors that are required for efficient influenza A virus (IAV) replication is essential to address questions related to pathogenicity and to identify targets for antiviral drug development. Here we focused on the interplay between IAV and DExD-box RNA helicases (DDX), which play a key role in cellular RNA metabolism by remodeling RNA-RNA or RNA-protein complexes. We performed a targeted RNAi screen on 35 human DDX proteins to identify those involved in IAV life cycle. DDX19 was a major hit. In DDX19-depleted cells the accumulation of viral RNAs and proteins was delayed, and the production of infectious IAV particles was strongly reduced. We show that DDX19 associates with intronless, unspliced and spliced IAV mRNAs and promotes their nuclear export. In addition, we demonstrate an RNA-independent association between DDX19 and the viral polymerase, that is modulated by the ATPase activity of DDX19. Our results provide a model in which DDX19 is recruited to viral mRNAs in the nucleus of infected cells to enhance their nuclear export. Information gained from this virus-host interaction improves the understanding of both the IAV replication cycle and the cellular function of DDX19.