MxB impedes the NUP358-mediated HIV-1 pre-integration complex nuclear import and viral replication cooperatively with CPSF6
Linlin Xie,
Lang Chen,
Chaojie Zhong,
Ting Yu,
Zhao Ju,
Meirong Wang,
Hairong Xiong,
Yan Zeng,
Jianhua Wang,
Haitao Hu,
Wei Hou,
Yong Feng
Affiliations
Linlin Xie
State Key Laboratory of Virology/Institute of Medical Virology/Hubei Province Key Laboratory of Allergy & Immunology, School of Basic Medical Sciences, Wuhan University
Lang Chen
State Key Laboratory of Virology/Institute of Medical Virology/Hubei Province Key Laboratory of Allergy & Immunology, School of Basic Medical Sciences, Wuhan University
Chaojie Zhong
State Key Laboratory of Virology/Institute of Medical Virology/Hubei Province Key Laboratory of Allergy & Immunology, School of Basic Medical Sciences, Wuhan University
Ting Yu
State Key Laboratory of Virology/Institute of Medical Virology/Hubei Province Key Laboratory of Allergy & Immunology, School of Basic Medical Sciences, Wuhan University
Zhao Ju
State Key Laboratory of Virology/Institute of Medical Virology/Hubei Province Key Laboratory of Allergy & Immunology, School of Basic Medical Sciences, Wuhan University
Meirong Wang
State Key Laboratory of Virology/Institute of Medical Virology/Hubei Province Key Laboratory of Allergy & Immunology, School of Basic Medical Sciences, Wuhan University
Hairong Xiong
State Key Laboratory of Virology/Institute of Medical Virology/Hubei Province Key Laboratory of Allergy & Immunology, School of Basic Medical Sciences, Wuhan University
Yan Zeng
Department of Zoology, College of Life Sciences, Nanjing Agriculture University
Jianhua Wang
Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences
Haitao Hu
Department of Microbiology and Immunology, Sealy Center for Vaccine Development and Institute for Human Infections and Immunity, University of Texas Medical Branch
Wei Hou
State Key Laboratory of Virology/Institute of Medical Virology/Hubei Province Key Laboratory of Allergy & Immunology, School of Basic Medical Sciences, Wuhan University
Yong Feng
State Key Laboratory of Virology/Institute of Medical Virology/Hubei Province Key Laboratory of Allergy & Immunology, School of Basic Medical Sciences, Wuhan University
Abstract Background 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. Results 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. Conclusions Our work establishes that MxB impedes the NUP358-mediated HIV-1 nuclear import and viral replication cooperatively with CPSF6.
