Human N-Alpha-Acetyltransferase 60 Promotes Influenza A Virus Infection by Dampening the Interferon Alpha Signaling.

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  • Author(s): Ahmed F;Ahmed F; Husain M; Husain M
  • Source:
    Frontiers in immunology [Front Immunol] 2022 Jan 12; Vol. 12, pp. 771792. Date of Electronic Publication: 2022 Jan 12 (Print Publication: 2021).
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Lausanne : Frontiers Research Foundation]
    • Subject Terms:
      Acetyltransferases/*metabolism ; Influenza A virus/*pathogenicity ; Influenza, Human/*metabolism ; Interferon-alpha/*metabolism ; Signal Transduction/*physiology; A549 Cells ; Acetylation ; Cell Line, Tumor ; Golgi Apparatus/metabolism ; Golgi Apparatus/virology ; Histones/metabolism ; Host-Pathogen Interactions/physiology ; Humans ; Membrane Proteins/metabolism ; Virus Replication/physiology
    • Abstract:
      N-alpha-acetyltransferase 60 (NAA60) is the most recently discovered N-terminal acetyltransferase and found only in multicellular eukaryotes. NAA60 localizes to the Golgi complex and is one of the only two N-terminal acetyltransferases known to localize to an organelle. Furthermore, NAA60 possesses a unique ability of catalyzing the acetylation of membrane-anchored proteins at the N-terminus and histones at the lysine side chains. Herein, we demonstrate that NAA60 exhibits proviral properties during influenza A virus (IAV) infection by interfering with the interferon (IFN) α signaling. We found that the depletion and overexpression of NAA60 reduced and enhanced, respectively, the IAV growth in a cell type- and IAV strain-independent manner. Mechanistically, the IAV-induced expression of IFNα was increased and decreased in NAA60-depleted and -overexpressing cells, respectively. Furthermore, the depletion of NAA60 enhanced the level of phosphorylated STAT1 transcription factor as well as the expression of several IFN-stimulated genes (ISGs) such as MX1, CH25H, IFITM3, ISG15 and viperin in infected cells. Whereas the overexpression of NAA60 produced opposite results. Finally, similar results were obtained when the NAA60-depleted cells were treated with purified IFNα. These findings, in conjunction with our recent findings where N-terminal acetylation of many host proteins increased in response to the IAV infection, indicate an important role of N-terminal acetylation during IAV replication.
      Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
      (Copyright © 2022 Ahmed and Husain.)
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    • Contributed Indexing:
      Keywords: CH25H; HAT; N-alpha-acetyltransferase 60; N-terminal acetylation; NAA60 gene; influenza virus; interferon α; viperin
    • Accession Number:
      0 (Histones)
      0 (Interferon-alpha)
      0 (Membrane Proteins)
      EC 2.3.1.- (Acetyltransferases)
    • Publication Date:
      Date Created: 20220131 Date Completed: 20220221 Latest Revision: 20220221
    • Publication Date:
      20240105
    • Accession Number:
      PMC8790067
    • Accession Number:
      10.3389/fimmu.2021.771792
    • Accession Number:
      35095845