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J Gen Virol. 2015 May 1. pii: vir.0.000171. doi: 10.1099/vir.0.000171. [Epub ahead of print]
The C-terminus of NS1 protein of influenza A/WSN/1933(H1N1) virus modulates antiviral responses in infected human macrophages and mice.
Anastasina M1, Schepens B2, S?derholm S3, Nyman TA4, Matikainen S3, Saksela K5, Saelens X2, Kainov DE1.
Author information
Abstract
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 NS1 gene. To understand the role of 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 WSN virus expressing NS1 with a 28 amino acids 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 amino acid truncation of NS1. Thus, our finding suggests 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.
PMID: 25934792 [PubMed - as supplied by publisher]
The C-terminus of NS1 protein of influenza A/WSN/1933(H1N1) virus modulates antiviral responses in infected human macrophages and mice.
Anastasina M1, Schepens B2, S?derholm S3, Nyman TA4, Matikainen S3, Saksela K5, Saelens X2, Kainov DE1.
Author information
Abstract
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 NS1 gene. To understand the role of 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 WSN virus expressing NS1 with a 28 amino acids 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 amino acid truncation of NS1. Thus, our finding suggests 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.
PMID: 25934792 [PubMed - as supplied by publisher]