Host genetic variants and gene expression patterns associated with Epstein-Barr virus copy number in lymphoblastoid cell lines.
Houldcroft, Charlotte J
Liu, Jimmy Z
Anderson, Carl A
Public Library of Science (PLoS)
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Houldcroft, C. J., Petrova, V., Liu, J. Z., Frampton, D., Anderson, C. A., Gall, A., & Kellam, P. (2014). Host genetic variants and gene expression patterns associated with Epstein-Barr virus copy number in lymphoblastoid cell lines.. PLoS One, 9 (10), e108384. https://doi.org/10.1371/journal.pone.0108384
Lymphoblastoid cell lines (LCLs) are commonly used in molecular genetics, supplying DNA for the HapMap and 1000 Genomes Projects, used to test chemotherapeutic agents, and informing the basis of a number of population genetics studies of gene expression. The process of transforming human B cells into LCLs requires the presence of Epstein-Barr virus (EBV), a double-stranded DNA virus which through B-cell immortalisation maintains an episomal virus genome in every cell of an LCL at variable copy numbers. Previous studies have reported that EBV alters host-gene expression and EBV copy number may be under host genetic control. We performed a genome-wide association study of EBV genome copy number in LCLs and found the phenotype to be highly heritable, although no individual SNPs achieved a significant association with EBV copy number. The expression of two host genes (CXCL16 and AGL) was positively correlated and expression of ADARB2 was negatively correlated with EBV copy number in a genotype-independent manner. This study shows an association between EBV copy number and the gene expression profile of LCLs, and suggests that EBV copy number should be considered as a covariate in future studies of host gene expression in LCLs.
B-Lymphocytes, Cell Line, Transformed, Humans, Herpesvirus 4, Human, Epstein-Barr Virus Infections, Gene Expression Regulation, Gene Dosage, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genetic Variation, Genome-Wide Association Study, Transcriptome
European Research Council (261213)
External DOI: https://doi.org/10.1371/journal.pone.0108384
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286193
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/