新乡医学院王辉教授团队在Ku70识别HTLV-1研究中取得进展

 

据了解，Ⅰ型病毒是目前发现的第一个与人类疾病相关的逆转录病毒，其感染所引发的成人T细胞白血病和强直性下肢轻瘫尚无有效的治疗手段。同时，宿主细胞抵抗Ⅰ型病毒感染的固有免疫应答反应目前还不清楚。

 

王辉团队发现，Ku70是一种新的Ⅰ型病毒识别受体。它可识别该反转中间体且调控人类T细胞白血病Ⅰ型病毒复制。Ku70在多种细胞中（尤其是固有免疫细胞中）可被Ⅰ型病毒感染诱导表达：过表达可抑制Ⅰ型病毒蛋白表达，诱发固有免疫应答反应；沉默则可促进Ⅰ型病毒蛋白表达，抑制固有免疫应答反应。同时，Ku70还可与Ⅰ型病毒的反转突变体ssDNA90相互作用：ssDNA90转染可诱导Ku70的表达，Ku70可促使ssDNA90诱导的固有免疫应答反应。

 

研究还显示，Ⅰ型病毒感染增强了Ku70和干扰素基因激活因子的相互作用，提示干扰素基因激活因子在Ku70介导的抗Ⅰ型病毒反应中具有重要功能。该项研究增加了对Ⅰ型病毒感染后病理情况的了解，对研究其他逆转录病毒感染后免疫事件的发生有很好的提示作用。

 

参考摘要：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 Ku70promoted 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.