Strong interferon-inducing capacity of a highly virulent variant of influenza A virus strain PR8 with deletions in the NS1 gene.
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.
Kochs
Georg
G
Department of Virology, University of Freiburg, D-79008 Freiburg, Germany.
Martínez-Sobrido
Luis
L
School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
Lienenklaus
Stefan
S
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Weiss
Siegfried
S
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
García-Sastre
Adolfo
A
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.
Staeheli
Peter
P
Department of Virology, University of Freiburg, D-79008 Freiburg, Germany.
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
C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta