Influenza virus infection causes global RNAPII termination defects.

Authors: Zhao, Nan and Sebastiano, Vittorio and Moshkina, Natasha and Mena, Nacho and Hultquist, Judd and Jimenez-Morales, David and Ma, Yixuan and Rialdi, Alex and Albrecht, Randy and Fenouil, Romain and Sánchez-Aparicio, Maria Teresa and Ayllon, Juan and Ravisankar, Sweta and Haddad, Bahareh and Ho, Jessica Sook Yuin and Low, Diana and Jin, Jian and Yurchenko, Vyacheslav and Prinjha, Rab K and Tarakhovsky, Alexander and Squatrito, Massimo and Pinto, Dalila and Allette, Kimaada and Byun, Minji and Smith, Melissa Laird and Sebra, Robert and Guccione, Ernesto and Tumpey, Terrence and Krogan, Nevan and Greenbaum, Benjamin and van Bakel, Harm and García-Sastre, Adolfo and Marazzi, Ivan

Viral infection perturbs host cells and can be used to uncover regulatory mechanisms controlling cellular responses and susceptibility to infections. Using cell biological, biochemical, and genetic tools, we reveal that influenza A virus (IAV) infection induces global transcriptional defects at the 3' ends of active host genes and RNA polymerase II (RNAPII) run-through into extragenic regions. Deregulated RNAPII leads to expression of aberrant RNAs (3' extensions and host-gene fusions) that ultimately cause global transcriptional downregulation of physiological transcripts, an effect influencing antiviral response and virulence. This phenomenon occurs with multiple strains of IAV, is dependent on influenza NS1 protein, and can be modulated by SUMOylation of an intrinsically disordered region (IDR) of NS1 expressed by the 1918 pandemic IAV strain. Our data identify a strategy used by IAV to suppress host gene expression and indicate that polymorphisms in IDRs of viral proteins can affect the outcome of an infection.

Journal: Nature structural & molecular biology
DOI: 10.1038/s41594-018-0124-7
Year: 2018

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