The role of nuclear NS1 protein in highly pathogenic H5N1 influenza viruses

Bobo Wing Yee Mok, Honglian Liu, Pin Chen, Siwen Liu, Siu Ying Lau, Xiaofeng Huang, Yen Chin Liu, Pui Wang, Kwok Yung Yuen, Honglin Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

14 Scopus citations

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.

Original languageEnglish
Pages (from-to)587-596
Number of pages10
JournalMicrobes and Infection
Volume19
Issue number12
DOIs
StatePublished - 12 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Institut Pasteur

Keywords

  • H5N1
  • HPAI
  • Influenza virus
  • NS1
  • Nuclear localization signal

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