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SV40 exploits the Nesprin-2-SUN1-KPNA4 axis for stepwise targeting and entry into the host nucleus to promote

Luke Gohmann, Billy Tsai

    Biorxiv : the Preprint Server for Biology
    |April 10, 2026
    PubMed

    Insights

    The SV40 virus enters the host cell nucleus by targeting the Nesprin-2 and SUN1 proteins at the nuclear membrane. This interaction facilitates viral entry through the nuclear pore complex via the KPNA4 importin receptor.

    Area of Science:

    • Virology
    • Cell Biology
    • Molecular Biology

    Background:

    • Nuclear entry is essential for DNA virus infection, but the mechanisms are not fully understood.
    • The polyomavirus SV40 (Simian virus 40) utilizes the Nesprin-2 protein for nuclear envelope targeting.

    Purpose of the Study:

    • To elucidate the host factors and mechanisms involved in SV40 nuclear import.
    • To investigate the role of SUN1 in SV40 nuclear targeting and entry.

    Main Methods:

    • Co-immunoprecipitation assays to study protein interactions.
    • Confocal microscopy to visualize viral and host protein localization.
    • Functional assays to assess viral nuclear entry.

    Main Results:

    • SUN1 acts coordinately with Nesprin-2 to target cytosolic SV40 to the nuclear membrane.
    • The SUN domain of SUN1 is critical for recruiting SV40 to the nuclear membrane.
    • SV40 binds to KPNA4 at the nuclear pore complex for translocation into the nucleus.

    Conclusions:

    • SV40 exploits the Nesprin-2-SUN1-KPNA4 axis for efficient nuclear entry.
    • This study reveals a novel pathway for DNA virus nuclear import.

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