MxB impedes the NUP358-mediated HIV-1 pre-integration complex nuclear import and viral replication cooperatively with CPSF6.

• 影响指数: 3.768
• 发表时间: 06 2020 29
• 来源期刊: Retrovirology
• DOI: 10.1186/s12977-020-00524-2
• PMID: 32600399
• 文章类型: Journal Article
• 中科院分区: Q3
• 方向: 医学
• 作者列表: Xie L,Chen L,Zhong C,Yu T,Ju Z,Wang M,Xiong H,Zeng Y,Wang J,Hu H,Hou W,Feng Y

关键词: CPSF6; HIV-1; MxB; Nuclear import; Nucleoporin

Mesh: Active Transport, Cell Nucleus; Capsid / metabolism; Capsid Proteins / genetics metabolism; Cell Nucleus / metabolism; HIV-1 / physiology; Humans; Indoles / pharmacology; Molecular Chaperones / genetics metabolism; Myxovirus Resistance Proteins / genetics metabolism; Nuclear Pore Complex Proteins / genetics metabolism; Phenylalanine / analogs & derivatives pharmacology; Protein Binding; Virus Replication; mRNA Cleavage and Polyadenylation Factors / genetics metabolism

Abstract

The 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.
We 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.
Our work establishes that MxB impedes the NUP358-mediated HIV-1 nuclear import and viral replication cooperatively with CPSF6.