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Article: Genomic diversity of Epstein-Barr virus genomes isolated from primary nasopharyngeal carcinoma biopsy samples

TitleGenomic diversity of Epstein-Barr virus genomes isolated from primary nasopharyngeal carcinoma biopsy samples
Authors
Issue Date2014
Citation
Journal of Virology, 2014, v. 88 n. 18, p. 10662-10672 How to Cite?
AbstractUndifferentiated nasopharyngeal carcinoma (NPC) has a 100% association with Epstein-Barr virus (EBV). However, only three EBV genomes isolated from NPC patients have been sequenced to date, and the role of EBV genomic variations in the pathogenesis of NPC is unclear. We sought to obtain the sequences of EBV genomes in multiple NPC biopsy specimens in the same geographic location in order to reveal their sequence diversity. Three published EBV (B95-8, C666-1, and HKNPC1) genomes were first resequenced using the sequencing workflow of target enrichment of EBV DNA by hybridization, followed by next-generation sequencing, de novo assembly, and joining of contigs by Sanger sequencing. The sequences of eight NPC biopsy specimen-derived EBV (NPC-EBV) genomes, designated HKNPC2 to HKNPC9, were then determined. They harbored 1,736 variations in total, including 1,601 substitutions, 64 insertions, and 71 deletions, compared to the reference EBV. Furthermore, genes encoding latent, early lytic, and tegument proteins and glycoproteins were found to contain nonsynonymous mutations of potential biological significance. Phylogenetic analysis showed that the HKNPC6 and -7 genomes, which were isolated from tumor biopsy specimens of advanced metastatic NPC cases, were distinct from the other six NPC-EBV genomes, suggesting the presence of at least two parental lineages of EBV among the NPC-EBV genomes. In conclusion, much greater sequence diversity among EBV isolates derived from NPC biopsy specimens is demonstrated on a whole-genome level through a complete sequencing workflow. Large-scale sequencing and comparison of EBV genomes isolated from NPC and normal subjects should be performed to assess whether EBV genomic variations contribute to NPC pathogenesis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/202735
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorKwok, Hen_US
dc.contributor.authorWu, CWen_US
dc.contributor.authorPalser, ALen_US
dc.contributor.authorKellam, Pen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorKwong, DLWen_US
dc.contributor.authorChiang, AKSen_US
dc.date.accessioned2014-09-19T09:33:29Z-
dc.date.available2014-09-19T09:33:29Z-
dc.date.issued2014en_US
dc.identifier.citationJournal of Virology, 2014, v. 88 n. 18, p. 10662-10672en_US
dc.identifier.urihttp://hdl.handle.net/10722/202735-
dc.description.abstractUndifferentiated nasopharyngeal carcinoma (NPC) has a 100% association with Epstein-Barr virus (EBV). However, only three EBV genomes isolated from NPC patients have been sequenced to date, and the role of EBV genomic variations in the pathogenesis of NPC is unclear. We sought to obtain the sequences of EBV genomes in multiple NPC biopsy specimens in the same geographic location in order to reveal their sequence diversity. Three published EBV (B95-8, C666-1, and HKNPC1) genomes were first resequenced using the sequencing workflow of target enrichment of EBV DNA by hybridization, followed by next-generation sequencing, de novo assembly, and joining of contigs by Sanger sequencing. The sequences of eight NPC biopsy specimen-derived EBV (NPC-EBV) genomes, designated HKNPC2 to HKNPC9, were then determined. They harbored 1,736 variations in total, including 1,601 substitutions, 64 insertions, and 71 deletions, compared to the reference EBV. Furthermore, genes encoding latent, early lytic, and tegument proteins and glycoproteins were found to contain nonsynonymous mutations of potential biological significance. Phylogenetic analysis showed that the HKNPC6 and -7 genomes, which were isolated from tumor biopsy specimens of advanced metastatic NPC cases, were distinct from the other six NPC-EBV genomes, suggesting the presence of at least two parental lineages of EBV among the NPC-EBV genomes. In conclusion, much greater sequence diversity among EBV isolates derived from NPC biopsy specimens is demonstrated on a whole-genome level through a complete sequencing workflow. Large-scale sequencing and comparison of EBV genomes isolated from NPC and normal subjects should be performed to assess whether EBV genomic variations contribute to NPC pathogenesis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.-
dc.languageengen_US
dc.relation.ispartofJournal of Virologyen_US
dc.subject.meshGenetic Variation-
dc.subject.meshHerpesvirus 4, Human - classification - genetics - isolation & purification-
dc.subject.meshNasopharyngeal Neoplasms - virology-
dc.titleGenomic diversity of Epstein-Barr virus genomes isolated from primary nasopharyngeal carcinoma biopsy samplesen_US
dc.typeArticleen_US
dc.identifier.emailKwok, H: hinkwok@hkucc.hku.hken_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.emailKwong, DLW: dlwkwong@hku.hken_US
dc.identifier.emailChiang, AKS: chiangak@hku.hken_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.identifier.authorityKwong, DLW=rp00414en_US
dc.identifier.authorityChiang, AKS=rp00403en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1128/JVI.01665-14-
dc.identifier.pmid24991008-
dc.identifier.pmcidPMC4178900-
dc.identifier.hkuros235983en_US
dc.identifier.volume88en_US
dc.identifier.issue18en_US
dc.identifier.spage10662-
dc.identifier.epage10672-
dc.customcontrol.immutablesml 150513-

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