Roles of lytic viral infection and IL-6 in early versus late passage lymphoblastoid cell lines and EBV-associated lymphoproliferative disease

Richard J. Jones, William T. Seaman, Wen Hei Feng, Elizabeth Barlow, Sarah Dickerson, Henri Jacque Delecluse, Shannon C. Kenney

    Research output: Contribution to journalArticlepeer-review

    54 Scopus citations

    Abstract

    Lytically infected EBV-positive lymphoblastoid cells enhance the growth of early-passage, but not late-passage, EBV-immortalized lymphoblastoid cell lines (LCLs) in SCID mice and have enhanced IL-6 secretion. Here, we have examined the importance of IL-6 for the growth of early-passage LCLs (EPL) in SCID mice, identified lytic EBV proteins that activate IL-6 production and compared viral and cellular differences between early versus late passage LCLs (LPL). IL-6 was required for efficient growth of EPL in SCID mice. The EBV immediate-early (IE) proteins, BRLF1 and BZLF1, each induced IL-6 secretion when transfected into 293 and BJAB cells. Interestingly, the combination of BZLF1 and the latent EBV protein, LMP-1, induced much more IL-6 expression in both 293 and BJAB cells than either protein alone. Both BZLF1 and BRLF1 also enhanced IL-10 production in 293 cells. In comparison to the EPL, LPL had much reduced expression of early lytic viral proteins and cellular IL-6. In contrast, expression of cellular IL-10 was similar in EPL versus LPL, while VEGF secretion was increased in late-passage LCLs. These results suggest that both BRLF1 and BZLF1 contribute to IL-6 secretion in lytically infected cells and that lytically infected cells may promote early lymphoproliferative disease in patients through enhanced IL-6 production.

    Original languageEnglish (US)
    Pages (from-to)1274-1281
    Number of pages8
    JournalInternational journal of cancer
    Volume121
    Issue number6
    DOIs
    StatePublished - Sep 15 2007

    Keywords

    • BRLF1
    • BZLF1
    • EBV
    • IL-6
    • LMP1
    • Lytic infection

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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