Properties of H7N7 influenza A virus strain SC35M lacking interferon antagonist NS1 in mice and chickens.
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.
Kochs
Georg
G
Department of Virology, University of Freiburg, 79104 Freiburg, Germany.
Koerner
Iris
I
Department of Virology, University of Freiburg, 79104 Freiburg, Germany.
Thiel
Lena
L
Institute for Virology, University of Marburg, Marburg, Germany.
Kothlow
Sonja
S
Institute for Animal Physiology, University of Munich, Munich, Germany.
Kaspers
Bernd
B
Institute for Animal Physiology, University of Munich, Munich, Germany.
Ruggli
Nicolas
N
Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland.
Summerfield
Artur
A
Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland.
Pavlovic
Jovan
J
Institute for Medical Virology, University of Zürich, Zürich, Switzerland.
Stech
Jürgen
J
Institute for Virology, University of Marburg, Marburg, Germany.
Staeheli
Peter
P
Department of Virology, University of Freiburg, 79104 Freiburg, Germany.
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
D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; D007372:Interferons