MxB impedes the NUP358-mediated HIV-1 pre-integration complex nuclear import and viral replication cooperatively with CPSF6
MxB impedes the NUP358-mediated HIV-1 pre-integration complex nuclear import and viral replication cooperatively with CPSF6
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MxB 与 CPSF6 协同阻止 NUP358 介导的 HIV-1 预整合复合体核输入和病毒复制
DOI：
10.1186/s12977-020-00524-2
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发表时间：
2020-06-29
期刊：
影响因子：
3.3
通讯作者：
Feng, Yong
中科院分区：
文献类型：
--
作者：
Xie, Linlin;Chen, Lang;Feng, Yong
背景人类粘病毒抗性2（humanmyxovirusresistance 2，Mx2/MxB）蛋白最初被发现调节细胞质-核转运，但最近报道其通过与HIV-1衣壳（capsid，CA）结合、阻止脱壳、前整合复合物（pre-integrationcomplex，PIC）的核输入和病毒DNA整合来限制HIV-1的复制。这项工作探讨了MxB介导的HIV-1 inhibition.ResultsWe的机制表明，MxB抑制NUP 358介导的PIC核输入和HIV-1复制。此外，MxB对PIC核输入和HIV-1复制的影响关键取决于辅因子切割和多聚腺苷酸化特异性因子亚基6（CPSF 6）。MxB结合核孔蛋白NUP 358，阻断NUP 358-CA相互作用，从而阻碍HIV-1 PIC与CPSF 6结合PIC的核输入。更有趣的是，CPSF 6的作用，在核进口依赖于MXB，是一个促进剂的HIV-1核进口本身，但成为一个抑制剂时，MXB是present.ConclusionsOur工作建立MXB阻碍NUP 358介导的HIV-1核进口和病毒复制与CPSF 6合作。
BackgroundThe human myxovirus resistance 2 (Mx2/MxB) protein was originally found to regulate cytoplasmic-nuclear transport but was recently reported to restrict HIV-1 replication by binding to HIV-1 capsid (CA), preventing uncoating, the nuclear import of pre-integration complex (PIC) and viral DNA integration. This work explores the mechanisms of MxB-mediated HIV-1 inhibition.ResultsWe demonstrated that MxB represses NUP358-mediated PIC nuclear import and HIV-1 replication. Moreover, MxB’s effects on PIC nuclear import and HIV-1 replication depend critically on cofactor cleavage and polyadenylation specificity factor subunit 6 (CPSF6). MxB binds nucleoporin NUP358, blocks NUP358-CA interaction, thereby impeding the nuclear import of HIV-1 PIC with CPSF6 binding to PIC. More intriguingly, CPSF6’s role in nuclear import depends on MxB, being a facilitator of HIV-1 nuclear import on its own, but becoming an inhibitor when MxB is present.ConclusionsOur work establishes that MxB impedes the NUP358-mediated HIV-1 nuclear import and viral replication cooperatively with CPSF6.