The C terminus of NS1 protein of influenza A/WSN/1933(H1N1) virus modulates antiviral responses in infected human macrophages and mice.
Non-structural protein NS1 of influenza A viruses interacts with cellular factors through its N-terminal RNA-binding, middle effector and C-terminal non-structured domains. NS1 attenuates antiviral responses in infected cells and thereby secures efficient virus replication. Some influenza strains express C-terminally truncated NS1 proteins due to nonsense mutations in the NS1 gene. To understand the role of the NS1 C-terminal region in regulation of antiviral responses, we engineered influenza viruses expressing C-terminally truncated NS1 proteins using A/WSN/33(H1N1) reverse genetics and tested them in human macrophages and in mice. We showed that a WSN virus expressing NS1 with a 28 aa deletion from its C terminus is a more powerful inducer of antiviral responses than the virus expressing full-length NS1, or one with a 10 aa truncation of NS1 in vitro. Thus, our findings suggest that the C-terminal region of NS1 is essential for regulation of antiviral responses. Moreover, viruses expressing truncated NS1 proteins could be good vaccine candidates.
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.
Maria
M
Anastasina
Inflammation Research Center, VIB, Ghent 9000, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent 9000, Belgium.
Bert
B
Schepens
Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki 00250, Finland.|The Institute of Biotechnology, University of Helsinki, FI- 00014, Finland.
Sandra
S
Söderholm
The Institute of Biotechnology, University of Helsinki, FI- 00014, Finland.
Tuula A
TA
Nyman
Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki 00250, Finland.
Sampsa
S
Matikainen
Department of Virology, Haartman Institute, University of Helsinki, Finland.
Kalle
K
Saksela
Inflammation Research Center, VIB, Ghent 9000, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent 9000, Belgium.
Xavier
X
Saelens
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00290, Finland.
Denis E
DE
Kainov
D020816:Amino Acid Motifs; D000818:Animals; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins