title: The NS1 protein of influenza A virus suppresses interferon-regulated activation of antigen-presentation and immune-proteasome pathways.
abstract: The NS1 protein of influenza virus counters host antiviral defences primarily by antagonizing the type I interferon (IFN) response. Both the N-terminal dsRNA-binding domain and the C-terminal effector domain are required for optimal suppression of host responses during infection. To better understand the regulatory role of the NS1 effector domain, we used an NS1-truncated mutant virus derived from human H1N1 influenza isolate A/Texas/36/91 (Tx/91) and assessed global transcriptional profiles from two independent human lung cell-culture models. Relative to the wild-type Tx/91-induced gene expression, the NS1 mutant virus induced enhanced expression of innate immune genes, specifically NF-κB signalling-pathway genes and IFN-α and -β target genes. We queried an experimentally derived IFN gene set to gauge the proportion of IFN-responsive genes that are suppressed specifically by NS1. We show that the C-terminally truncated NS1 mutant virus is less efficient at suppressing IFN-regulated gene expression associated with activation of antigen-presentation and immune-proteasome pathways. This is the first report integrating genomic analysis from two independent human culture systems, including primary lung cells, using genetically similar H1N1 influenza viruses that differ only in the length of the NS1 protein.
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Jennifer R
authors: JR
authors: Tisoncik
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Rosalind
authors: R
authors: Billharz
authors: Department of Microbiology, Mount Sinai School of Medicine, New York, NY, USA.
authors: Svetlana
authors: S
authors: Burmakina
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Sarah E
authors: SE
authors: Belisle
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Sean C
authors: SC
authors: Proll
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Marcus J
authors: MJ
authors: Korth
authors: Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY, USA.|Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, NY, USA.|Department of Microbiology, Mount Sinai School of Medicine, New York, NY, USA.
authors: Adolfo
authors: A
authors: García-Sastre
authors: Washington National Primate Research Center, University of Washington, Seattle, WA 98195, USA.|Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Michael G
authors: MG
authors: Katze
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