Epstein-Barr virus (EBV) is a ubiquitous pathogen of humans that can cause several types of lymphoma and carcinoma. Like other herpesviruses, EBV has diversified both through co-evolution with its host, and genetic exchange between virus strains. Sequence analysis of the EBV genome is unusually challenging, because of the large number and length of repeat regions within the virus. Here we describe the sequence assembly and analysis of the large internal repeat of EBV (IR1 or BamW repeats) from over 70 strains.Diversity of the latency protein EBNA-LP resides predominantly within the exons downstream of IR1. The integrity of the putative BWRF1 ORF is retained in over 80% of strains, and deletions truncating IR1 always spare BWRF1. Conserved regions include the IR1 latency promoter (Wp), and one zone upstream of and two within BWRF1.IR1 is heterogeneous in 70% of strains, and this heterogeneity arises from sequence exchange between strains as well as spontaneous mutation, with inter-strain recombination more common in tumour-derived viruses. This genetic exchange often incorporates regions of <1kb, and allelic gene conversion changes the frequency of small regions within repeat, but not close to flanks. these observations suggest that ir1 - by extension ebv diversifies through both recombination breakpoint repair, while concerted evolution is driven regions. finally, prototype strain b95-8 contains four non-consensus variants a single repeat unit, including stop codon in ebna-lp. repairing improves ebna-lp levels quality transformation bac.importance epstein-barr virus (ebv) infects majority world population, only causes illness minority. nevertheless, over 1% cancers worldwide are attributable ebv. recent sequencing projects investigating diversity, see if different strains have disease impacts, excluded repeating sequence, as they more technically challenging. here we analyse sequence largest (ir1). first characterised variations protein sequences encoded across ir1. studying each strain, identified mutation main laboratory impairs function, tumour-associated viruses may be likely contain dna mixed from two strains. patterns this mixing can spread between (and also repeat) copying another (or unit) repair damage. copyright © 2017 ba abdullah et al.
Journal: Journal of virology
DOI: 10.1128/JVI.00920-17
Year: 2017