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Article: Genomic sequencing and comparative analysis of Epstein-Barr virus genome isolated from primary nasopharyngeal carcinoma biopsy

TitleGenomic sequencing and comparative analysis of Epstein-Barr virus genome isolated from primary nasopharyngeal carcinoma biopsy
Authors
KeywordsBLF4 gene
BLLF1 gene
BLLF2 gene
BOLF1 gene
CD8+ T lymphocyte
Issue Date2012
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2012, v. 7 n. 5 How to Cite?
AbstractWhether certain Epstein-Barr virus (EBV) strains are associated with pathogenesis of nasopharyngeal carcinoma (NPC) is still an unresolved question. In the present study, EBV genome contained in a primary NPC tumor biopsy was amplified by Polymerase Chain Reaction (PCR), and sequenced using next-generation (Illumina) and conventional dideoxy-DNA sequencing. The EBV genome, designated HKNPC1 (Genbank accession number JQ009376) is a type 1 EBV of approximately 171.5 kb. The virus appears to be a uniform strain in line with accepted monoclonal nature of EBV in NPC but is heterogeneous at 172 nucleotide positions. Phylogenetic analysis with the four published EBV strains, B95-8, AG876, GD1, and GD2, indicated HKNPC1 was more closely related to the Chinese NPC patient-derived strains, GD1 and GD2. HKNPC1 contains 1,589 single nucleotide variations (SNVs) and 132 insertions or deletions (indels) in comparison to the reference EBV sequence (accession number NC007605). When compared to AG876, a strain derived from Ghanaian Burkitt's lymphoma, we found 322 SNVs, of which 76 were non-synonymous SNVs and were shared amongst the Chinese GD1, GD2 and HKNPC1 isolates. We observed 88 non-synonymous SNVs shared only by HKNPC1 and GD2, the only other NPC tumor-derived strain reported thus far. Non-synonymous SNVs were mainly found in the latent, tegument and glycoprotein genes. The same point mutations were found in glycoprotein (BLLF1 and BALF4) genes of GD1, GD2 and HKNPC1 strains and might affect cell type specific binding. Variations in LMP1 and EBNA3B epitopes and mutations in Cp (11404 C>T) and Qp (50134 G>C) found in GD1, GD2 and HKNPC1 could potentially affect CD8 + T cell recognition and latent gene expression pattern in NPC, respectively. In conclusion, we showed that whole genome sequencing of EBV in NPC may facilitate discovery of previously unknown variations of pathogenic significance. © 2012 Kwok et al.
Persistent Identifierhttp://hdl.handle.net/10722/152649
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council GRFHKU763208M
EBV Research of AKSC20004525
University of Hong Kong to the Genome Research Centre
University of Hong Kong
HoTung Paediatrics Education and Research Fund
Funding Information:

This study was funded by Research Grant Council GRF grant HKU763208M and EBV Research grant 20004525 of AKSC and a grant from the University Development Fund of the University of Hong Kong to the Genome Research Centre. HK was supported by The University of Hong Kong's postgraduate studentship and HoTung Paediatrics Education and Research Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorKwok, Hen_HK
dc.contributor.authorTong, AHYen_HK
dc.contributor.authorLin, CHen_HK
dc.contributor.authorLok, Sen_HK
dc.contributor.authorFarrell, PJen_HK
dc.contributor.authorKwong, DLWen_HK
dc.contributor.authorChiang, AKSen_HK
dc.date.accessioned2012-07-16T09:45:14Z-
dc.date.available2012-07-16T09:45:14Z-
dc.date.issued2012en_HK
dc.identifier.citationPlos One, 2012, v. 7 n. 5en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/152649-
dc.description.abstractWhether certain Epstein-Barr virus (EBV) strains are associated with pathogenesis of nasopharyngeal carcinoma (NPC) is still an unresolved question. In the present study, EBV genome contained in a primary NPC tumor biopsy was amplified by Polymerase Chain Reaction (PCR), and sequenced using next-generation (Illumina) and conventional dideoxy-DNA sequencing. The EBV genome, designated HKNPC1 (Genbank accession number JQ009376) is a type 1 EBV of approximately 171.5 kb. The virus appears to be a uniform strain in line with accepted monoclonal nature of EBV in NPC but is heterogeneous at 172 nucleotide positions. Phylogenetic analysis with the four published EBV strains, B95-8, AG876, GD1, and GD2, indicated HKNPC1 was more closely related to the Chinese NPC patient-derived strains, GD1 and GD2. HKNPC1 contains 1,589 single nucleotide variations (SNVs) and 132 insertions or deletions (indels) in comparison to the reference EBV sequence (accession number NC007605). When compared to AG876, a strain derived from Ghanaian Burkitt's lymphoma, we found 322 SNVs, of which 76 were non-synonymous SNVs and were shared amongst the Chinese GD1, GD2 and HKNPC1 isolates. We observed 88 non-synonymous SNVs shared only by HKNPC1 and GD2, the only other NPC tumor-derived strain reported thus far. Non-synonymous SNVs were mainly found in the latent, tegument and glycoprotein genes. The same point mutations were found in glycoprotein (BLLF1 and BALF4) genes of GD1, GD2 and HKNPC1 strains and might affect cell type specific binding. Variations in LMP1 and EBNA3B epitopes and mutations in Cp (11404 C>T) and Qp (50134 G>C) found in GD1, GD2 and HKNPC1 could potentially affect CD8 + T cell recognition and latent gene expression pattern in NPC, respectively. In conclusion, we showed that whole genome sequencing of EBV in NPC may facilitate discovery of previously unknown variations of pathogenic significance. © 2012 Kwok et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectBLF4 gene-
dc.subjectBLLF1 gene-
dc.subjectBLLF2 gene-
dc.subjectBOLF1 gene-
dc.subjectCD8+ T lymphocyte-
dc.titleGenomic sequencing and comparative analysis of Epstein-Barr virus genome isolated from primary nasopharyngeal carcinoma biopsyen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1932-6203&volume=7&spage=e36939&epage=&date=2012&atitle=Genomic+Sequencing+and+Comparative+Analysis+of+Epstein-Barr+Virus+Genome+Isolated+from+Primary+Nascopharyngeal+Carcinoma+Biopsyen_US
dc.identifier.emailLok, S: silok@genome.hku.hken_HK
dc.identifier.emailChiang, AKS: chiangak@hku.hken_HK
dc.identifier.authorityLok, S=rp00271en_HK
dc.identifier.authorityChiang, AKS=rp00403en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0036939en_HK
dc.identifier.pmid22590638-
dc.identifier.pmcidPMC3349645-
dc.identifier.scopuseid_2-s2.0-84860994450en_HK
dc.identifier.hkuros200658en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84860994450&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume7en_HK
dc.identifier.issue5en_HK
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000305336400048-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridKwok, H=55216823800en_HK
dc.identifier.scopusauthoridTong, AHY=55216611200en_HK
dc.identifier.scopusauthoridLin, CH=44761160100en_HK
dc.identifier.scopusauthoridLok, S=21035019900en_HK
dc.identifier.scopusauthoridFarrell, PJ=7201756081en_HK
dc.identifier.scopusauthoridKwong, DLW=54890371000en_HK
dc.identifier.scopusauthoridChiang, AKS=7101623534en_HK
dc.identifier.citeulike10721415-

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