RT info:eu-repo/semantics/article
T1 Influenza virus infection causes global RNAPII termination defects
A1 Zhao, Nan
A1 Sebastiano, Vittorio
A1 Moshkina, Natasha
A1 Mena, Nacho
A1 Hultquist, Judd
A1 Jimenez-Morales, David
A1 Ma, Yixuan
A1 Rialdi, Alex
A1 Albrecht, Randy
A1 Fenouil, Romain
A1 Sánchez-Aparicio, M. T.
A1 Ayllón Barasoain, Juan
A1 Ravisankar, Sweta
A1 Haddad, Bahareh
A1 Ho, Sook-Yiun
A1 Low, Diana
A1 Jin, Jian
A1 Yurchenko, Vyacheslav
A1 Prinjha, Rab K.
A1 Tarakhovsky, Alexander
A1 Squatrito, Massimo
A1 Pinto, Dalila
A1 Kimaada, Allette
A1 Byun, Minji
A1 Smith, Melissa Laird
A1 Sebra, Robert
A1 Guccione, Ernesto
A1 Tumpey, Terrence
A1 Krogan, Nevan
A1 Greenbaum, Benjamin
A1 van Bakel, Harm
A1 García Sastre, Adolfo
A1 Marazzi, Ivan
K1 Virus
K1 Poli ADP ribosa polimerasa
K1 NAD-ADP-ribosyltransferase
AB 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.
PB Nature Research
SN 1545-9993
YR 2018
FD 2018-09
LK https://hdl.handle.net/10259/10919
UL https://hdl.handle.net/10259/10919
LA eng
NO We thank all members of the laboratories of I.M. and A.G.-S., and J. Bloom and A. Kornblihtt for valuable discussions and suggestions on the manuscript. We thank the Medicinal Chemistry Core, Integrated Screening Core, Microscopy CoRE,, and Global Health and Emerging Pathogens Institute (GHEPI) at the Icahn School of Medicine at Mount Sinai. H.v.B., I.M., and A.G.-S. are partially supported by HHSN272201400008C–Center for Research on Influenza Pathogenesis (CRIP), a NIAID-funded Center of Excellence for Influenza Research and Surveillance (CEIRS). I.M. is supported in part by the Department of Defense W911NF-14-1-0353. I.M. and H.v.B. are supported by NIH grant 1R01AN3663134. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai.
DS Repositorio Institucional de la Universidad de Burgos
RD 27-abr-2026