This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xue, S.-A. Articles by Griffin, B. E. Search for Related Content PubMed PubMed Citation Articles by Xue, S.-A. Articles by Griffin, B. E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2003, p. 2192-2201, Vol. 23, No. 6
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.6.2192-2201.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Genetic Diversity: Frameshift Mechanisms Alter Coding of a Gene (Epstein-Barr Virus LF3 Gene) That Contains Multiple 102-Base-Pair Direct Sequence Repeats

Viral Oncology Unit, Division of Medicine, Wright-Fleming Institute, Imperial College of Science, Technology and Medicine at St. Mary's, London W2 1PG,¹ Department of Infectious Diseases, Imperial College Faculty of Medicine,³ Clinical Sciences Centre, Medical Research Council, Hammersmith Hospital, London W12 0NN, United Kingdom,⁴ College of Life Sciences, Shaanxi Normal University, Xian 710062, People's Republic of China,² Department of Pathology, Free University of Amsterdam, Amsterdam, The Netherlands⁵

Received 6 September 2002/ Returned for modification 7 October 2002/ Accepted 17 December 2002

Frameshift mutations provide recognized mechanisms for changing the coding potential of an organism. Here, multiple frameshifts are identified in repetitive sequences within an Epstein-Barr virus unspliced early gene, LF3, which is associated with the viral replicative cycle and also transcriptionally expressed in many virally associated tumors. On the DNA strand encoding LF3, there are three open reading frames, only one of which contains an initiation codon. Most (>95%) of the gene consists of numerous (>20, varying with cell source) GC-rich copies of a 102-bp direct repeat (called IR 4) flanked by small unique sequences. LF3 may express a protein if its initiation and termination codons reside in the same reading frame, but this is not always the case. Frameshifting events, occurring in short runs of pyrimidines (mainly C residues) in the repeats, give rise to mutations which may provide a mechanism for escape of an LF3 function from host surveillance. Sequence studies link these frameshifts to DNA replication errors. Notably, the number of sites in LF3 at which such mutations can occur permits a very large amount of diversity in this gene. Our data also suggest a second degeneracy mechanism within the protein itself, which influences its stability and may reflect a host defense mechanism. LF3 thus provides a potentially important model for studying the quest for supremacy between a virus and its host.

This article has been cited by other articles:

• Xue, S.-A., Griffin, B. E. (2007). Complexities associated with expression of Epstein-Barr virus (EBV) lytic origins of DNA replication. Nucleic Acids Res 35: 3391-3406 [Abstract] [Full Text]