Genome-wide analysis of wild-type epstein-barr virus genomes derived from healthy individuals of the 1000 genomes project

Abstract

Most people in the world (~90%) are infected by the Epstein-Barr virus (EBV), which establishes itself permanently in B-cells. Infection by EBV is related to a number of diseases including infectious mononucleosis, multiple sclerosis and different types of cancer. So far, only seven complete EBV strains have been described, all of them coming from donors presenting EBV-related diseases.

To perform a detailed comparative genomics analysis of EBV including, for the first time, EBV strains derived from healthy individuals we reconstructed EBV sequences infecting lymphoblastoid cell lines (LCLs) from the 1000 Genomes Project. Since strain B95-8 was used to transform B-cells to obtain LCLs, it is always present, but a specific deletion in its genome sets it apart from natural EBV strains. After studying hundreds of individuals, we determined the presence of natural EBV in at least 10 of them and obtained a set of variants specific to wild-type EBV. By mapping the natural EBV reads into the EBV reference genome (NC007605) we constructed wild-type viral genomes from three individuals.

Analysis of all the available sequences reveals a complex history of recombination among EBV strains and that latency genes harbour more nucleotide diversity than lytic genes. Six out of nine latency-related genes present the molecular signature of positive selection, suggesting rapid host-parasite co-evolution.