Genetic factors affecting EBV Load in Transformed LCLs from the 1000 Genome Project: a GWAS on Transformation

Abstract

Worldwide, >90% of the adult population is infected by the Epstein-Barr virus (EBV), which has been an evolutionary companion of our lineage for millions of years. EBV remains within the host after primary infection and can cause mononucleosis. There is also evidence linking it with multiple sclerosis and different types of tumors. Although the EBV has been the focus of extensive research work, much remain s unknown about what makes some individuals more sensitive to EBV infection and to adverse outcomes as a result of infection. The EBV is used to transform B-cells into lymphoblastoid cell lines (LCLs). We hypothesized that differences among individual LCLs in the EBV load resulting from EBV transformation may reflect different genetic susceptibility to EBV infection. To test this hypothesis, we retrieved whole-genome sequenced LCL reads 2215 samples sequenced within the 1000 Genome Project and derived from 26 different populations worldwide. We subjected these samples to in silico viral load estimation, and the accuracy was validated by RT-PCR. Our results showed considerable differences in viral load among populations, while no significant difference was observed between males and females. The proper estimation of EBV load has made it possible to perform a genome wide association analysis (GWAS) between estimated EBV load and genetic variants determined within the 1000 genome project samples. GWAS yielded many putative candidate genes that necessitate further evaluation to reveal the biological mechanisms underlying EBV load and EBV associated diseases.