Multiple pathways for Epstein-Barr virus episome loss from nasopharyngeal carcinoma.
Epstein-Barr virus (EBV) is the prototypical example for episomal persistence of genetic information. Yet, little is known about how this viral episome is lost. Episome loss occurs naturally in nasopharyngeal carcinoma (NPC) upon explantation into culture. Using whole-genome profiling, we found evidence for 2 different pathways of episome loss: (i) rapid loss of the entire episome or (ii) successive mutation/deletion of the episome until at least 1 essential cis-element is destroyed. This second phenotype was seen in a clone of HONE-1 NPC cells that maintains the EBV episome for prolonged time in culture. The conceptual insights provided by our quantitative analysis should aid our understanding of mammalian episomes, as well as lead to designs to cure latent viral infection.
Dittmer
Dirk P
DP
Lineberger Comprehensive Cancer Center, Center for AIDS Research and Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA. ddittmer@med.unc.edu
Hilscher
Chelsey J
CJ
Gulley
Margaret L
ML
Yang
Eric V
EV
Chen
Min
M
Glaser
Ronald
R
D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000032:analysis; D018628:Gene Dosage; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000821:virology*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic
D004279:DNA, Viral