Induction of Cytokines and Cytotoxic Molecules with the Expression of Latent Epstein-Barr Virus Infection Genes in Human T-cell Lines

In chronic active Epstein-Barr virus (EBV) (CAEBV) disease, EBV infects T or natural killer cells, and patients frequently develop life-threatening complications, such as EBV-associated hemophagocytic lymphohistiocytosis, which is characterized by the excessive release of cytokines such as interleukins (ILs), interferons, and chemokines and leads to multiple organ failure. We have introduced a plasmid containing the coding sequences of EBV-encoded small RNAs (EBERs) or latent membrane protein (LMP) 1, or both plasmids into human T-lymphocyte virus-I-negative human T-cell lines using an expression plasmid vector harboring EBV nuclear antigen 1 and established stable transformants. Here, we evaluated the modification of cytokine expression by the latent EBV genes, EBERs and LMP1, in these stable transformants. The expression of tumor necrosis factor α, perforin, and IL-10 increased with the introduction of both EBERs and LMP1 at both the mRNA and protein levels in CCRF-HSB2 cells, an immature T-cell line without cell surface protein expression of both the TCRα/β and TCRγ/δ. EBV latent infection genes, EBERs and LMP1, would be responsible for the pathogenesis of CAEBV disease. CCRF-HSB2 would be useful for the further analyses of these intracellular mechanisms in T-lineage cells and the pathogenesis of CAEBV disease. Shinshu Med J 74 : 101―109, 2026