title: Strong interferon-inducing capacity of a highly virulent variant of influenza A virus strain PR8 with deletions in the NS1 gene.
abstract: Influenza viruses lacking the interferon (IFN)-antagonistic non-structural NS1 protein are strongly attenuated. Here, we show that mutants of a highly virulent variant of A/PR/8/34 (H1N1) carrying either a complete deletion or C-terminal truncations of NS1 were far more potent inducers of IFN in infected mice than NS1 mutants derived from standard A/PR/8/34. Efficient induction of IFN correlated with successful initial virus replication in mouse lungs, indicating that the IFN response is boosted by enhanced viral activity. As the new NS1 mutants can be handled in standard biosafety laboratories, they represent convenient novel tools for studying virus-induced IFN expression in vivo.
authors.affiliation: Department of Virology, University of Freiburg, D-79008 Freiburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Kochs
authors.affiliation: School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Sobrido
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lienenklaus
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Departments of Microbiology and Medicine (Division of Infectious Diseases) and Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Department of Virology, University of Freiburg, D-79008 Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
mesh_terms: D000818:Animals; D017353:Gene Deletion; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D016899:Interferon-beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication
chemical_list: C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta