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Microbes Infect. 2017 Sep 10. pii: S1286-4579(17)30142-9. doi: 10.1016/j.micinf.2017.08.011. [Epub ahead of print]
The role of nuclear NS1 protein in highly pathogenic H5N1 influenza viruses.
Mok BW1, Liu H1, Chen P1, Liu S1, Lau SY1, Huang X1, Liu YC1, Wang P1, Yuen KY1, Chen H2.
Author information
Abstract
The non-structural protein (NS1) of influenza A viruses (IAV) performs multiple functions during viral infection. NS1 contains two nuclear localization signals (NLS): NLS1 and NLS2. The NS1 protein is located predominantly in the nucleus during the early stages of infection and subsequently exported to the cytoplasm. A nonsense mutation that results in a large deletion in the carboxy-terminal region of the NS1 protein that contains the NLS2 domain was found in some IAV subtypes, including highly pathogenic avian influenza (HPAI) H7N9 and H5N1 viruses. We introduced different mutations into the NLS domains of NS1 proteins in various strains of IAV, and demonstrated that mutation of the NLS2 region in the NS1 protein of HPAI H5N1 viruses severely affects its nuclear localization pattern. H5N1 viruses expressing NS1 protein that is unable to localize to the nucleus are less potent in antagonizing cellular antiviral responses than viruses expressing wild-type NS1. However, no significant difference was observed with respect to viral replication and pathogenesis. In contrast, the replication and antiviral defenses of H1N1 viruses are greatly attenuated when nuclear localization of the NS1 protein is blocked. Our data reveals a novel functional plasticity for NS1 proteins among different IAV subtypes.
Copyright ? 2017. Published by Elsevier Masson SAS.
KEYWORDS:
H5N1; HPAI; Influenza virus; NS1; nuclear localization signal
PMID: 28903072 DOI: 10.1016/j.micinf.2017.08.011
The role of nuclear NS1 protein in highly pathogenic H5N1 influenza viruses.
Mok BW1, Liu H1, Chen P1, Liu S1, Lau SY1, Huang X1, Liu YC1, Wang P1, Yuen KY1, Chen H2.
Author information
Abstract
The non-structural protein (NS1) of influenza A viruses (IAV) performs multiple functions during viral infection. NS1 contains two nuclear localization signals (NLS): NLS1 and NLS2. The NS1 protein is located predominantly in the nucleus during the early stages of infection and subsequently exported to the cytoplasm. A nonsense mutation that results in a large deletion in the carboxy-terminal region of the NS1 protein that contains the NLS2 domain was found in some IAV subtypes, including highly pathogenic avian influenza (HPAI) H7N9 and H5N1 viruses. We introduced different mutations into the NLS domains of NS1 proteins in various strains of IAV, and demonstrated that mutation of the NLS2 region in the NS1 protein of HPAI H5N1 viruses severely affects its nuclear localization pattern. H5N1 viruses expressing NS1 protein that is unable to localize to the nucleus are less potent in antagonizing cellular antiviral responses than viruses expressing wild-type NS1. However, no significant difference was observed with respect to viral replication and pathogenesis. In contrast, the replication and antiviral defenses of H1N1 viruses are greatly attenuated when nuclear localization of the NS1 protein is blocked. Our data reveals a novel functional plasticity for NS1 proteins among different IAV subtypes.
Copyright ? 2017. Published by Elsevier Masson SAS.
KEYWORDS:
H5N1; HPAI; Influenza virus; NS1; nuclear localization signal
PMID: 28903072 DOI: 10.1016/j.micinf.2017.08.011