In Vivo Effects of the Epstein–Barr Virus Small RNA EBER-1 on Protein Synthesis and Cell Growth Regulation

• Published in: Virology (New York, N.Y.) Vol. 297; no. 2; pp. 253 - 269
• Main Authors: Laing, Kenneth G., Elia, Androulla, Jeffrey, Ian, Matys, Volker, Tilleray, Vivienne J., Souberbielle, Bernard, Clemens, Michael J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.06.2002
• Subjects: Animals; Cell Division; Cell Line; Cell Line, Transformed; Cell Transformation, Viral; EBER-1 RNA; eIF-2 Kinase - metabolism; Epstein–Barr virus; fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Fibroblasts - virology; Gene Expression Regulation; growth regulation; Herpesvirus 4, Human - pathogenicity; Humans; malignant transformation; Mice; Neoplasms - physiopathology; Protein Biosynthesis; protein kinase R; protein synthesis; RNA, Viral - physiology; Transfection; tumourigenesis; fibroblasts; tumourigenesis; malignant transformation; transfection; protein synthesis; growth regulation; Epstein–Barr virus; EBER-1 RNA; protein kinase R
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.2002.1354

Recent studies have suggested a role for the Epstein–Barr virus-encoded RNA EBER-1 in malignant transformation. EBER-1 inhibits the activity of the protein kinase PKR, an inhibitor of protein synthesis with tumour suppressor properties. In human 293 cells and murine embryonic fibroblasts, transient expression of EBER-1 promoted total protein synthesis and enhanced the expression of cotransfected reporter genes. However reporter gene expression was stimulated equally well in cells from control and PKR knockout mice. NIH 3T3 cells stably expressing EBER-1 exhibited a greatly increased frequency of colony formation in soft agar, and protein synthesis in these cells was relatively resistant to inhibition by the calcium ionophore A23187. Nevertheless clones containing a high concentration of EBER-1 were not invariably tumourigenic. We conclude that EBER-1 can enhance protein synthesis by a PKR-independent mechanism and that, although this RNA may contribute to the oncogenic potential of Epstein–Barr virus, its expression is not always sufficient for malignant transformation.