Immune evasion by HIV-1 protease-mediated cleavage of TANK-binding kinase1

逆转录病毒已经进化出有效的策略来逃避宿主免疫应答，从而允许连续和有效的病毒复制。我们研究了HIV-1蛋白酶对免疫信号传导的修饰作用。利用小麦无细胞蛋白质合成系统和放大发光邻近均相分析（AlphaScreen），我们发现TANK结合激酶1（TBK 1）是HIV-1蛋白酶的底物。我们进一步发现HIV-1蛋白酶切割TBK 1的C-末端结构域，这种作用可以削弱TBK 1对IRF-3磷酸化和INFβ启动子反式激活的功能。这些结果共同表明，HIV-1蛋白酶可能通过靶向TBK 1破坏先天免疫信号传导，导致逃避抗病毒免疫应答。

Retroviruses have evolved effective strategies to evade the host immune response thereby allowing continuous and efficient viral replication. We investigated the action of the HIV-1 protease on the modification of immune signaling. Using the wheat cell-free protein synthesis system and the amplified luminescent proximity homogeneous assay (AlphaScreen), we found that TANK-binding kinase 1 (TBK1) is a substrate for HIV-1 protease. We further revealed that HIV-1 protease cleaved the C-terminal domain of TBK1 and this effect can impair the function of TBK1 for the phosphorylation of IRF-3 and the transactivation of INFβ promoter. These results together indicate that HIV-1 protease may disrupt the innate immune signaling via targeting TBK1 leading to escape from the anti-viral immune response.