Possible involvement in oncogenesis of a single base mutation in an internal ribosome entry site of Epstein-Barr nuclear antigen 1 mRNA.
It has been reported recently that the U leader exon located within the 5' untranslated region of Epstein-Barr nuclear antigen 1 (EBNA1) gene contains an internal ribosome entry site (IRES) element. Sequence analysis of the U leader exon was undertaken in samples from 19 patients with infectious mononucleosis and 19 patients with lethal lymphoproliferative diseases and in 15 spontaneously established lymphoblastoid cell lines. The sequence was conserved except for a single base substitution (T-C) at position 67,585. Although the mutation was detected in only one case of infectious mononucleosis, it was found in more than half of the lethal lymphoproliferative diseases and all lymphoblastoid cell lines. The results suggest that a mutation in the IRES element affects EBNA1 gene expression at the translational level and provides Epstein-Barr virus (EBV)-infected cells with a growth advantage, leading to immortalization of cells in vitro and to the development of lethal lymphoproliferative diseases in vivo.
Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
Rika
R
Endo
Hideaki
H
Kikuta
Takashi
T
Ebihara
Nobuhisa
N
Ishiguro
Kunihiko
K
Kobayashi
D020121:5' Untranslated Regions / Q000235:genetics*; D018929:Cell Culture Techniques; D002471:Cell Transformation, Neoplastic; D004279:DNA, Viral / Q000737:chemistry / Q000302:isolation & purification; D020031:Epstein-Barr Virus Infections / Q000235:genetics*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D005091:Exons; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity*; D015616:Histiocytosis, Non-Langerhans-Cell / Q000821:virology*; D006801:Humans; D007244:Infectious Mononucleosis / Q000821:virology; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000502:physiology; D017422:Sequence Analysis, DNA
D020121:5' Untranslated Regions; D004279:DNA, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; C417029:EBV-encoded nuclear antigen 1