Influenza B mutant viruses with truncated NS1 proteins grow efficiently in Vero cells and are immunogenic in mice.
Contemporary influenza B virus strains were generated encoding C-terminally truncated NS1 proteins. Viable viruses containing the N-terminal 14, 38, 57 or 80 aa of the NS1 protein were rescued in Vero cells. The influenza B virus NS1-truncated mutants were impaired in their ability to counteract interferon (IFN) production, induce antiviral pro-inflammatory cytokines early after infection and show attenuated or restricted growth in IFN-competent hosts. In Vero cells, all of the mutant viruses replicated to high titres comparable to the wild-type influenza B virus. Mice that received a single, intranasal immunization of the NS1-truncated mutants elicited an antibody response and protection against wild-type virus challenge. Therefore, these NS1-truncated mutants should prove useful as potential candidates for live-attenuated influenza virus vaccines.
Wressnigg
Nina
N
University of Vienna, Institute of Microbiology and Genetics, Dr Bohrgasse 9, 1030 Vienna, Austria.|Avir Greenhills Biotechnology, Gersthoferstrasse 29-31, 1180 Vienna, Austria.
Shurygina
Anna Polina
AP
Influenza Research Institute, Russian Academy of Medical Sciences, Prof. Popov Str. 15/17, St Petersburg 197376, Russia.|Avir Greenhills Biotechnology, Gersthoferstrasse 29-31, 1180 Vienna, Austria.
Wolff
Thorsten
T
Robert Koch Institute, P15, Nordufer 20, 13353 Berlin, Germany.
Redlberger-Fritz
Monika
M
Clinical Institute for Virology, Medical University of Vienna, Kinderspitalgasse 15, 1090 Vienna, Austria.
Popow-Kraupp
Therese
T
Department of Dermatology, Medical University of Vienna, Währinger Gurtel 18-20, 1090 Vienna, Austria.
Muster
Thomas
T
Department of Dermatology, Medical University of Vienna, Währinger Gurtel 18-20, 1090 Vienna, Austria.|Avir Greenhills Biotechnology, Gersthoferstrasse 29-31, 1180 Vienna, Austria.
Egorov
Andrej
A
Avir Greenhills Biotechnology, Gersthoferstrasse 29-31, 1180 Vienna, Austria.
Kittel
Christian
C
Avir Greenhills Biotechnology, Gersthoferstrasse 29-31, 1180 Vienna, Austria.
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D009981:Influenza B virus / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007370:Interferon Type I / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D051379:Mice / Q000821:virology*; D017384:Sequence Deletion; D014162:Transfection; D014613:Vaccines, Attenuated / Q000276:immunology*; D014709:Vero Cells / Q000821:virology*; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014779:Virus Replication
D016207:Cytokines; C085820:INS1 protein, influenza virus; D007252:Influenza Vaccines; D007370:Interferon Type I; D016898:Interferon-alpha; D014613:Vaccines, Attenuated; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta