Influenza virus NS1 protein binds cellular DNA to block transcription of antiviral genes.
Influenza NS1 protein is an important virulence factor that is capable of binding double-stranded (ds) RNA and inhibiting dsRNA-mediated host innate immune responses. Here we show that NS1 can also bind cellular dsDNA. This interaction prevents loading of transcriptional machinery to the DNA, thereby attenuating IAV-mediated expression of antiviral genes. Thus, we identified a previously undescribed strategy, by which RNA virus inhibits cellular transcription to escape antiviral response and secure its replication.
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland; Institute of Biotechnology, University of Helsinki, 00014, Finland.
Maria
M
Anastasina
Department of Functional Genomics and Cancer, Institute for genetics, molecular and cellular biology (IGBMC), Strasbourg 67404, France.
Nicolas
N
Le May
Medicum, Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki FIN-00014, Finland.
Andrii
A
Bugai
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.
Yu
Y
Fu
Institute of Biotechnology, University of Helsinki, 00014, Finland.
Sandra
S
Söderholm
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.
Lana
L
Gaelings
Institute of Biotechnology, University of Helsinki, 00014, Finland.
Tiina
T
Ohman
National Institute for Health and Welfare (THL), Helsinki 00271, Finland.
Janne
J
Tynell
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.
Suvi
S
Kyttänen
Medicum, Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki FIN-00014, Finland.
Matjaz
M
Barboric
Institute of Biotechnology, University of Helsinki, 00014, Finland; Institute of Clinical Medicine, Sognsvannsveien 20, Rikshospitalet, 0372 Oslo, Norway.
Tuula A
TA
Nyman
Medicum, Department of Biochemistry and Developmental Biology, University of Helsinki, Helsinki FIN-00014, Finland.
Sampsa
S
Matikainen
National Institute for Health and Welfare (THL), Helsinki 00271, Finland; Department of Virology, University of Turku, Turku 20014, Finland.
Ilkka
I
Julkunen
Institute of Biotechnology, University of Helsinki, 00014, Finland.
Sarah J
SJ
Butcher
Department of Functional Genomics and Cancer, Institute for genetics, molecular and cellular biology (IGBMC), Strasbourg 67404, France. Electronic address: egly@igbmc.fr.
Jean-Marc
JM
Egly
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland. Electronic address: denis.kainov@helsinki.fi.
Denis E
DE
Kainov
D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000502:physiology; D011485:Protein Binding; D014158:Transcription, Genetic / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000378:metabolism* / Q000502:physiology; D014779:Virus Replication
D002843:Chromatin; C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D004247:DNA
Antiviral responses; Influenza A virus; Innate immunity; Regulation of gene expression; Viral counter-responses