Schlafen 14 (SLFN14) is a novel antiviral factor involved in the control of viral replication

Immunobiology. 2017 Nov;222(11):979-988. doi: 10.1016/j.imbio.2017.07.002. Epub 2017 Jul 11.

Abstract

Schlafen (SLFN) proteins have been suggested to play important functions in cell proliferation and immune cell development. In this study, we determined the antiviral activities of putative RNA-helicase domain-containing SLFN14. Murine SLFN14 expression was specifically induced by TLR3-mediated pathways and type I interferon (IFN) in RAW264.7 mouse macrophages. To examine the role of SLFN during viral infection, cells were infected with either wild-type PR8 or delNS1/PR8 virus. SLFN14 expression was specifically induced following influenza virus infection. Overexpression of SLFN14 in A549 cells reduced viral replication, whereas knockdown of SLFN14 in RAW264.7 cells enhanced viral titers. Furthermore, SLFN14 promoted the delay in viral NP translocation from cytoplasm to nucleus and enhanced RIG-I-mediated IFN-β signaling. In addition, SLFN14 overexpression promoted antiviral activity against varicella zoster virus (VZV), a DNA virus. In conclusion, our data suggest that SLFN14 is a novel antiviral factor for both DNA and RNA viruses.

Keywords: Anti-viral; Influenza; Interferon; SLFN14; VZV.

MeSH terms

  • A549 Cells
  • Animals
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism*
  • Epithelial Cells / physiology*
  • Epithelial Cells / virology
  • Gene Expression Regulation
  • Herpesvirus 3, Human / physiology*
  • Humans
  • Immunity
  • Infection Control
  • Influenza A virus / physiology*
  • Influenza, Human / immunology*
  • Macrophages / physiology*
  • Macrophages / virology
  • Mice
  • Orthomyxoviridae Infections / immunology*
  • RAW 264.7 Cells
  • RNA Helicases / genetics*
  • RNA Helicases / metabolism
  • RNA, Small Interfering / genetics
  • Receptors, Retinoic Acid / metabolism
  • Signal Transduction
  • Varicella Zoster Virus Infection / immunology*
  • Virus Replication*

Substances

  • PLAAT4 protein, human
  • RNA, Small Interfering
  • Receptors, Retinoic Acid
  • Endoribonucleases
  • SLFN14 protein, human
  • Slfn14 protein, mouse
  • RNA Helicases