Ku70 Senses HTLV-1 DNA and Modulates HTLV-1 Replication

J Immunol. 2017 Oct 1;199(7):2475-2482. doi: 10.4049/jimmunol.1700111. Epub 2017 Aug 18.


Human T lymphotropic virus type 1 (HTLV-1) belongs to the deltaretrovirus family and has been linked to multiple diseases. However, the innate host defense against HTLV-1 is unclear. In this study, we report that the expression of Ku70, a known DNA sensor against DNA viruses, could be induced by HTLV-1 infection in HeLa, PMA-differentiated THP1 cells, primary human monocytes, and human monocyte-derived macrophages. In these cells, the overexpression of Ku70 inhibited the HTLV-1 protein expression, whereas the knockdown of Ku70 promoted the HTLV-1 protein expression. Furthermore, the overexpression of Ku70 enhanced the cellular response to HTLV-1 infection, whereas Ku70 knockdown yielded the opposite effect. Additionally, Ku70 was found to interact with HTLV-1 reverse transcription intermediate ssDNA90. ssDNA90 stimulation induced Ku70 expression and Ku70 promoted ssDNA90-triggered innate immune responses. Finally, HTLV-1 infection enhanced the association between Ku70 and stimulator of IFN genes, suggesting that stimulator of IFN genes was involved in Ku70-mediated host defenses against HTLV-1 infection. Taken together, our findings suggest a new sensor that detects HTLV-1 reverse transcription intermediate and controls HTLV-1 replication. These findings may provide new angles to understand host defenses against HTLV-1 infection and HTLV-1-associated diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • DNA, Viral*
  • Gene Products, tax / genetics
  • HeLa Cells
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / immunology
  • Human T-lymphotropic virus 1 / physiology*
  • Humans
  • Immunity, Innate
  • Interferons / genetics
  • Interferons / immunology
  • Ku Autoantigen / deficiency
  • Ku Autoantigen / genetics*
  • Ku Autoantigen / immunology
  • Ku Autoantigen / metabolism*
  • Macrophages / virology
  • Monocytes / virology
  • Virus Replication*
  • gag Gene Products, Human Immunodeficiency Virus / genetics


  • DNA, Viral
  • Gene Products, tax
  • gag Gene Products, Human Immunodeficiency Virus
  • p19 protein, Human T-lymphotropic virus 1
  • Interferons
  • Ku Autoantigen