title: Properties of H7N7 influenza A virus strain SC35M lacking interferon antagonist NS1 in mice and chickens.
abstract: Non-structural protein NS1 of influenza A virus counteracts the host immune response by blocking the synthesis of type I interferon (IFN). As deletion of the complete NS1 gene has to date been reported only in the human H1N1 strain A/PR/8/34, it remained unclear whether NS1 is a non-essential virulence factor in other influenza A virus strains as well. In this report, the properties of NS1-deficient mutants derived from strain SC35M (H7N7) are described. A mutant of SC35M that completely lacks the NS1 gene was an excellent inducer of IFN in mammalian and avian cells in culture and, consequently, was able to multiply efficiently only in cell lines with defects in the type I IFN system. Virus mutants carrying C-terminally truncated versions of NS1 were less powerful inducers of IFN and were attenuated less strongly in human A549 cells. Although attenuated in wild-type mice, these mutants remained highly pathogenic for mice lacking the IFN-regulated antiviral factor Mx1. In contrast, the NS1-deficient SC35M mutant was completely non-pathogenic for wild-type mice, but remained pathogenic for mice lacking Mx1 and double-stranded RNA-activated protein kinase (PKR). Wild-type SC35M, but not the NS1-deficient mutant virus, was able to replicate in the upper respiratory tract of birds, but neither virus induced severe disease in adult chickens. Altogether, this study supports the view that NS1 represents a non-essential virulence factor of different influenza A viruses.
authors.affiliation: Department of Virology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Kochs
authors.affiliation: Department of Virology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Koerner
authors.affiliation: Institute for Virology, University of Marburg, Marburg, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Thiel
authors.affiliation: Institute for Animal Physiology, University of Munich, Munich, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kothlow
authors.affiliation: Institute for Animal Physiology, University of Munich, Munich, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kaspers
authors.affiliation: Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ruggli
authors.affiliation: Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland.
authors.forename: Artur
authors.initials: A
authors.lastname: Summerfield
authors.affiliation: Institute for Medical Virology, University of Zürich, Zürich, Switzerland.
authors.forename: Jovan
authors.initials: J
authors.lastname: Pavlovic
authors.affiliation: Institute for Virology, University of Marburg, Marburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Stech
authors.affiliation: Department of Virology, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D002522:Chlorocebus aethiops; D004285:Dogs; D006801:Humans; D053126:Influenza A Virus, H7N7 Subtype / Q000145:classification / Q000302:isolation & purification / Q000502:physiology*; D005585:Influenza in Birds / Q000276:immunology*; D007251:Influenza, Human; D016899:Interferon-beta / Q000235:genetics; D007372:Interferons / Q000037:antagonists & inhibitors; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000172:deficiency*; D014774:Virulence
chemical_list: D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; D007372:Interferons