Effect of EBV-transformation on Oxidative Phosphorylation Physiology in Human Cell lines

Abstract

AO_SCPLOWBSTRACTC_SCPLOWDo the immortalized and cryopreserved white blood cells that are part of the 1,000 Human Genomes Project represent a valuable cellular physiological resource to investigate the importance of genome wide sequence variation? While much research exists on the nucleotide variation in the 1,000 Human Genomes, there are few quantitative measures of these humans physiologies. Fortunately, physiological measures can be done on the immortalized and preserved cells from each of the more than 1,000 individuals that are part of Human Genome project. However, these human white blood cells were immortalized by transforming them with the Epstein-Barr virus (EBV-transformed lymphoblastoid cell lines (LCL)). This transformation integrates the viral genome into the human genome and potentially affects important biological differences among individuals. The questions we address here are whether EBV transformations significantly alters the cellular physiology so that 1) replicate transformations within an individual are significantly different, and 2) whether the variance among replicates obscures the variation among individuals. To address these questions, we quantified oxidative phosphorylation (OxPhos) metabolism in LCLs from six individuals with 4 separate and independent EBV-transformations. We examined OxPhos because it is critical for energy production, and mutations in this pathway are responsible for most inborn metabolic diseases. The data presented here demonstrate that there are small but significant effects of EBV-transformations on some OxPhos parameters. In spite of significant variation due to transformations, there is greater and significant variation among individuals in their OxPhos metabolism. Thus, the LCLs from the 1,000 Human Genome project could provide valuable insights into the natural variation of cellular physiology because there is statistically significant variation among individuals when using these EBV-transformed cells.