IFI16 regulates HTLV-1 replication through promoting HTLV-1 RTI-induced innate immune responses

FEBS Lett. 2018 May;592(10):1693-1704. doi: 10.1002/1873-3468.13077. Epub 2018 May 14.

Abstract

Interferon (IFN)-inducible protein 16 (IFI16) regulates human immunodeficiency virus replication by inducing innate immune responses as a DNA sensor. Human T-lymphotropic virus type 1 (HTLV-1), a delta retrovirus family member, has been linked to multiple diseases. Here, we report that IFI16 expression is induced by HTLV-1 infection or HTLV-1 reverse transcription intermediate (RTI) ssDNA90 transfection. IFI16 overexpression decreases HTLV-1 protein expression, whereas IFI16 knockdown increases it. Furthermore, the knockdown of IFI16 is followed by impaired innate immune responses upon HTLV-1 infection. In addition, IFI16 forms a complex with ssDNA90 and enhances ssDNA90-triggered innate immune responses. Collectively, our data suggest a critical role for IFI16 during HTLV-1 infection by interacting with HTLV-1 RTI ssDNA90 and restricting HTLV-1 replication.

Keywords: DNA sensor; HTLV-1; IFI16; innate immune responses; reverse transcription intermediate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DNA, Single-Stranded / genetics
  • DNA, Viral / genetics
  • Gene Knockdown Techniques
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / physiology*
  • Humans
  • Immunity, Innate / physiology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Viral Proteins / genetics
  • Virus Replication / physiology*

Substances

  • DNA, Single-Stranded
  • DNA, Viral
  • Nuclear Proteins
  • Phosphoproteins
  • Viral Proteins
  • IFI16 protein, human