Regulation of Sp100A subnuclear localization and transcriptional function by EBNA-LP and interferon.
Epstein-Barr virus (EBV) efficiently immortalizes human B cells and is associated with several human malignancies. The EBV transcriptional activating protein EBNA2 and the EBNA2 coactivator EBNA-leader protein (EBNA-LP) are important for B cell immortalization. Recent observations from our laboratory indicate that EBNA-LP coactivation function is mediated through interactions with the interferon-inducible gene (ISG) Sp100, resulting in displacement from its normal location in promyelocytic leukemia nuclear bodies (PML NBs) into the nucleoplasm. The EBNA-LP- and interferon-mediated mechanisms that regulate Sp100 subnuclear localization and transcriptional function remain undefined. To clarify these issues, we generated a panel of Sp100 mutant proteins to ascertain whether EBNA-LP induces Sp100 displacement from PML NBs by interfering with Sp100 dimerization or through other domains. In addition, we tested EBNA-LP function in interferon-treated cells. Our results indicate that Sp100 dimerization, PML NB localization, and EBNA-LP interaction domains overlap significantly. We also show that IFN-beta does not inhibit EBNA-LP coactivation function. The results suggest that EBNA-LP might play a role in EBV-evasion of IFN-mediated antiviral responses.
Echendu
Chisaroka W
CW
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
Ling
Paul D
PD
D034961:Antigens, Nuclear / Q000235:genetics* / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism* / Q000821:virology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport; D011994:Recombinant Proteins; D017384:Sequence Deletion; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D034961:Antigens, Nuclear; D001324:Autoantigens; C402640:EBNA-LP protein, Human herpesvirus 4; D011994:Recombinant Proteins; D014764:Viral Proteins; C066642:SP100 protein, human; D007372:Interferons