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Genome-Wide Analysis of Epstein-Barr Virus Isolated from Extra Nodal NK/T-Cell Lymphoma, Nasal Type

Abstract

Wenjing Ku, Ningjing Lin and Zheming Lu

Extra-nodal natural killer (NK) cell/T cell lymphoma (NKTCL), a rare type of non-Hodgkin’s lymphoma, has strongly been associated with Epstein-Barr virus (EBV) infection. However, there is no EBV genomes isolated from NKTCL, and the roles of the variations of EBV strains played in the pathogenesis of NKTCL is still unclear. In this study, whole EBV genomes from eight primary NKTCL biopsy specimens were obtained using next generation sequencing, designated NKTCL-EBV1 to 8. Compared to the six mostly referenced EBV strains, NKTCL-EBVs were closely resemble to GD1 strain, but still harbors 2072 variations, including 1938 substitutions, 58 insertions and 76 deletions. Moreover, the results from phylogenetic analysis of whole NKTCL genomes and specific genes demonstrated that all the NKTCL-EBVs were related to Asian EBV strains. Furthermore, changes in CD4+ and CD8+ T-cell epitopes of EBNA1 and LMP1 may affect the efficacy for a CTL-based therapy. In conclusion, this is the first large study to our knowledge to obtain EBV genomes isolated from NKTCL and show the diversity of EBV genomes in a whole genome level by phylogenetic analysis.

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