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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number16
JournalRetrovirology
Volume17
Issue number1
DOIs
StatePublished - Jun 29 2020

Keywords

  • CPSF6
  • HIV-1
  • MxB
  • Nuclear import
  • Nucleoporin

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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    Xie, L., Chen, L., Zhong, C., Yu, T., Ju, Z., Wang, M., Xiong, H., Zeng, Y., Wang, J., Hu, H., Hou, W., & Feng, Y. (2020). MxB impedes the NUP358-mediated HIV-1 pre-integration complex nuclear import and viral replication cooperatively with CPSF6. Retrovirology, 17(1), [16]. https://doi.org/10.1186/s12977-020-00524-2