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

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

Author information

1
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China.
2
Xinxiang Assegai Medical Laboratory Institute, Xinxiang 453003, China.
3
Department of Laboratory Medicine, Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, China; and.
4
Research Center for Immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China ybb@mail.ustc.edu.cn huiwang65@yeah.net.
5
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China; ybb@mail.ustc.edu.cn huiwang65@yeah.net.

Abstract

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.

PMID:
28821586
DOI:
10.4049/jimmunol.1700111
[Indexed for MEDLINE]

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