Ubiquitin-specific protease 9X in host cells interacts with herpes simplex virus 1 ICP0

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  • SATO Yuka
    Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan
  • KATO Akihisa
    Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan
  • ARII Jun
    Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan
  • KOYANAGI Naoto
    Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan
  • KOZUKA-HATA Hiroko
    Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan
  • OYAMA Masaaki
    Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan
  • KAWAGUCHI Yasushi
    Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108–8639, Japan

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Herpes simplex virus 1 (HSV-1) expresses infected cell protein 0 (ICP0), a multi-functional protein with E3 ubiquitin ligase activity and a critical regulator of the viral life cycle. To obtain novel insights into the molecular mechanism by which ICP0 regulates HSV-1 replication, we analyzed HEp-2 cells infected with HSV-1 by tandem affinity purification and mass spectrometry-based proteomics. This screen identified 50 host-cell proteins that potentially interact with ICP0, including ubiquitin-specific protease 9X (USP9X). The interaction between ICP0 and USP9X was confirmed by co-immunoprecipitation. Notably, USP9X depletion increased the ICP0 abundance and promoted viral replication. These results suggest that USP9X-dependent regulation of ICP0 expression is part of a complex feedback mechanism that facilitates optimal HSV-1 replication.

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