differential expression of human A549 cell upon infection with IAV SC35M wt and SC35M NS1 184-188 mutant

A functional NS1 effector domain is essential for the defect in 3 termination of host transcriptionIAV infection provokes a global deregulation of RNA-Pol II transcription termination by impairing 3-end cleavage and termination (10,11,12). We here infected cells with wildtype IAV (SC35M) and mutant IAV NS1 184 -188 for six hours and then investigated the host cell transcriptome by RNASeq analysis.The alignment of the reads to the human model genome confirms the deregulation of RNA-Pol II transcription termination upon wildtype IAV infection. However, comparing transcriptional termination in wildtype infected cells and mutant NS1 184 -188 infected cells revealed that no deregulation of 3 termination of host transcription could be observed in cells infected with the mutant IAV NS1 184-188 confirming that the effector domain of NS1 is also responsible and sufficient for the deregulation of the 3 termination of host cell transcription. Additionally, usually non-transcribed regions of the genome as pseudogenes are transcribed in cells infected with wildtype IAV but not when infected with IAV NS1 184-188 . The deregulation does not uniformly affect all genes. As seen in figure 7D the transcriptional termination of the histone genes is hardly altered. These findings are largely in agreement with recent reports (10,11,12).