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Updated: Mar 1, 2026

Using Reverse Genetics to Manipulate the NSs Gene of the Rift Valley Fever Virus MP-12 Strain to Improve Vaccine Safety and Efficacy
Published on: November 1, 2011
Residues F103 and M106 within the influenza A virus NS1 CPSF4-binding region regulate interferon-stimulated gene
Ben X Wang1, Earl G Brown2, Eleanor N Fish1
1Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8; Toronto General Hospital Research Institute, University Health Network, 67 College Street, Room 424, Toronto, Ontario, Canada M5G 2M1.
Abstract:
Influenza A virus (IAV) non-structural protein 1 (NS1) suppresses host innate immune responses by inhibiting type I interferon (IFN) production. We provide evidence that residues F103 and M106 in the CPSF4-binding domain of A/HK/1/68 [H3N2] NS1 contribute to post-transcriptional inhibition of antiviral IFN-stimulated genes (ISGs), thereby suppressing an antiviral type I IFN response. Recombinant (r) IAVs encoding F103L and M106I mutations in NS1 replicate to significantly lower viral titers in human A549 lung epithelial cells and primary type II alveolar cells. In A549 cells, rIAVs encoding these mutant NS1s induce higher levels of IFN-β production and are more sensitive to the antiviral effects of IFN-β treatment. qPCR characterization of polysomal mRNA, in the presence or absence of IFN-β treatment, identified a greater proportion of heavy polysome-associated ISGs including EIF2AK2, OAS1, and MxA in A549 cells infected with rIAVs encoding these CPSF4-binding mutant NS1s, in contrast to rIAV encoding wildtype NS1.
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