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

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• The myxovirus resistance 2 (MxB) protein is known to regulate transport between the cytoplasm and nucleus.
• MxB was recently found to restrict HIV-1 replication by binding to the viral capsid, inhibiting uncoating and nuclear import.

Purpose of the Study:

• To investigate the mechanisms by which MxB inhibits HIV-1 replication.
• To elucidate the role of MxB in the context of nuclear import and viral DNA integration.

Main Methods:

• Investigated the interaction between MxB, NUP358, and HIV-1 pre-integration complex (PIC).
• Assessed the impact of MxB on NUP358-mediated PIC nuclear import.
• Examined the dependence of MxB's inhibitory effects on cofactor cleavage and polyadenylation specificity factor subunit 6 (CPSF6).

Main Results:

• MxB was shown to repress NUP358-mediated PIC nuclear import and HIV-1 replication.
• MxB's inhibitory function was found to critically depend on CPSF6.
• MxB binds to NUP358, blocking the interaction with HIV-1 capsid (CA) and impeding PIC nuclear import, especially when CPSF6 is bound to the PIC.
• CPSF6's role in nuclear import is modulated by MxB; it facilitates import alone but inhibits it in MxB's presence.

Conclusions:

• MxB impedes NUP358-mediated HIV-1 nuclear import and viral replication.
• MxB cooperates with CPSF6 to inhibit HIV-1 nuclear import and replication, highlighting a novel antiviral mechanism.