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Barrier-to-autointegration factor 1 promotes gammaherpesvirus reactivation from latency

Author

Listed:
  • Grant Broussard

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Guoxin Ni

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Zhigang Zhang

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Qian Li

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Patricio Cano

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Dirk P. Dittmer

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Blossom Damania

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

Abstract

Gammaherpesviruses, including Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are DNA viruses that are globally associated with human cancers and establish lifelong latency in the human population. Detection of gammaherpesviral infection by the cGAS-STING innate immune DNA-sensing pathway is critical for suppressing viral reactivation from latency, a process that promotes viral pathogenesis and transmission. We report that barrier-to-autointegration factor 1 (BAF)-mediated suppression of the cGAS-STING signaling pathway is necessary for reactivation of KSHV and EBV. We demonstrate a role for BAF in destabilizing cGAS expression and show that inhibiting BAF expression in latently infected, reactivating, or uninfected cells leads to increased type I interferon-mediated antiviral responses and decreased viral replication. Furthermore, BAF overexpression resulted in decreased cGAS expression at the protein level. These results establish BAF as a key regulator of the lifecycle of gammaherpesviruses and a potential target for treating viral infections and malignancies.

Suggested Citation

  • Grant Broussard & Guoxin Ni & Zhigang Zhang & Qian Li & Patricio Cano & Dirk P. Dittmer & Blossom Damania, 2023. "Barrier-to-autointegration factor 1 promotes gammaherpesvirus reactivation from latency," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35898-2
    DOI: 10.1038/s41467-023-35898-2
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