Regulation of influenza a virus mRNA splicing by CLK1

Publication date: Available online 6 June 2019Source: Antiviral ResearchAuthor(s): Anita Artarini, Michael Meyer, Yu Jin Shin, Kilian Huber, Nikolaus Hilz, Franz Bracher, Daniel Eros, Laszlo Orfi, Gyorgy Keri, Sigrid Goedert, Martin Neuenschwander, Jens von Kries, Yael Domovich-Eisenberg, Noa Dekel, István Szabadkai, Mario Lebendiker, Zoltán Horváth, Tsafi Danieli, Oded Livnah, Olivier MoncorgéAbstractInfluenza A virus carries eight negative single-stranded RNAs and uses spliced mRNAs to increase the number of proteins produced from them. Several genome-wide screens for essential host factors for influenza A virus replication revealed a necessity for splicing and splicing-related factors, including Cdc-like kinase 1 (CLK1). This CLK family kinase plays a role in alternative splicing regulation through phosphorylation of serine-arginine rich (SR) proteins. To examine the influence that modulation of splicing regulation has on influenza infection, we analyzed the effect of CLK1 knockdown and inhibition. CLK1 knockdown in A549 cells reduced influenza A/WSN/33 virus replication and increased the level of splicing of segment 7, encoding the viral M1 and M2 proteins. CLK1−/− mice infected with influenza A/England/195/2009 (H1N1pdm09) virus supported lower levels of virus replication than wild-type mice. Screening of newly developed CLK inhibitors revealed several compounds that have an effect on the level of splicing of influenza A gene segment M in different models and d...
Source: Antiviral Therapy - Category: Virology Source Type: research