Latency-associated nuclear antigen inhibits lytic replication of Kaposi's sarcoma-associated herpesvirus by regulating let-7a/RBPJ signaling
Latency-associated nuclear antigen inhibits lytic replication of Kaposi's sarcoma-associated herpesvirus by regulating let-7a/RBPJ signaling
复制标题
潜伏相关核抗原通过调节let-7a/RBPJ信号抑制卡波西肉瘤相关疱疹病毒的裂解性复制
DOI：
10.1016/j.virol.2019.02.019
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发表时间：
2019-05-01
期刊：
影响因子：
3.7
通讯作者：
Yang, Lei
中科院分区：
文献类型：
--
作者：
Qi, Yan;Zheng, Guoxia;Yang, Lei
潜伏相关核抗原（拉娜）是卡波济肉瘤相关疱疹病毒（KSHV）潜伏期建立和维持的关键因素。免疫球蛋白κ J区重组信号结合蛋白（RBPJ）是KSHV裂解激活所必需的细胞蛋白。然而，RBPJ的表达是否受KSHV的调控尚不清楚。在这里，我们表明，拉娜上调let-7 a和它的主要成绩单在其减少RBPJ表达平行。notch胞内结构域（NICD）的增加以及NF-κ B和LIN 28 B的下调有助于拉娜上调let-7 a。Let-7a通过直接结合RBPJ的3 '非翻译区来抑制RBPJ表达。Let-7a过表达或RBPJ敲低导致KSHV裂解再激活的剂量和时间依赖性抑制。总的来说，这些发现支持一个模型，其中拉娜通过调节let-7 a/RBPJ信号传导抑制KSHV的裂解复制。
Latency-associated nuclear antigen (LANA) is the key factor in the establishment and maintenance of latency of Kaposi's sarcoma-associated herpesvirus (KSHV). A cellular protein, recombination signal binding protein for immunoglobulin kappa J region (RBPJ), is essential for the lytic reactivation of KSHV. However, whether RBPJ expression is regulated by KSHV is not clear. Here, we show that LANA upregulates let-7a and its primary transcripts in parallel with its reduction of RBPJ expression. An increase in notch intracellular domain (NICD) and the downregulation of NF-kappa B and LIN28B contribute to the upregulation of let-7a by LANA. Let-7a represses RBPJ expression by directly binding the 3' untranslated region of RBPJ. Let-7a overexpression or RBPJ knockdown led to a dose- and time-dependent inhibition of lytic reactivation of KSHV. Collectively, these findings support a model wherein LANA inhibits the lytic replication of KSHV by regulating let-7a/RBPJ signaling.