title: Comparative analysis of 22 Epstein-Barr virus genomes from diseased and healthy individuals.
abstract: Epstein-Barr virus (EBV) infects most of the world's population and is causally associated with several human cancers, but little is known about how EBV genetic variations might influence EBV-associated diseases and their geographical patterns. In the present study, 22 EBV whole-genome sequences from diseased and healthy individuals were analysed to explore EBV sequence variations at the whole-genome level. We found that the 22 EBV genomes were generally highly similar to each other at the genome level. However, varying degrees of genetic diversity were detected across the entire genome, especially in the latent genes. In contrast, the sequences of promoters and non-coding RNAs were strictly conserved. These findings suggested that both latent genes and non-coding RNAs play important roles in the EBV life cycle. When we investigated changes in known T-cell epitopes in some latent and lytic proteins, we observed that some T-cell epitopes were changed, while others were conserved. These findings indicate that the effect of EBV variations in protein sequences that seem to have been selected by the host immune system should be considered when conducting EBV-targeted immunotherapy. Taken together, our results provide a global view of EBV genome sequence variation, which not only is important for designing vaccines and immunotherapy for EBV but also adds to the understanding of EBV biology and the relationships between viral sequence variation and EBV-associated diseases.
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, PR China.
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Chen
authors.affiliation: DRIGEN Co. Ltd, No. 121-122 Chuangye Yuan, Shenzhen 518100, PR China.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Qiu
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, PR China.
authors.forename: Yu-Hang
authors.initials: YH
authors.lastname: Pan
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, PR China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, PR China.
authors.forename: Chun-Kui
authors.initials: CK
authors.lastname: Shao
mesh_terms: D002353:Carrier State / Q000821:virology*; D016000:Cluster Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000821:virology*; D014644:Genetic Variation; D016679:Genome, Viral; D064368:Healthy Volunteers; D004854:Herpesvirus 4, Human / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D010802:Phylogeny; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
chemical_list: D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte