Phylogenetic comparison of the first complete EBV genomes sequenced and analyzed in Argentina

BERENSTEIN, A; MARIA VICTORIA PRECIADO; BLAZQUEZ, C.; LORENZETTI, M.; IZQUIERDO, A.

Montreal

Simposio; 16th ISCB Student Council Symposium (SCS); 2020

International Society for Computational Biology

Background: Epstein Barr Virus (EBV) infects more than 90% of the population and can be related to benign and malignant conditions. EBV-related malignancies prevalence, proportion of EBV associated cases and viral types (EBV1 and EBV2) circulation vary among geographical regions. Given NGS methods, more than 800 worldwide complete genomes were sequenced; however, South American EBV isolates are underrepresented. Our aim was to characterize polymorphisms in the entire genome of EBV isolates from our region and compare them with sequences from different geographies.Description: Fifteen isolates from Argentinian pediatric patients were sequenced by NGS methods using EBV custom target enrichment probes. To compare the variability in the context of EBV sequences from other geographies, 203 publicly available raw-NGS data were downloaded from SRA-NCBI database. All the fastq files were analysed with our custom-built mapping-based bioinformatic pipeline. After the preprocessing steps, reads were mapped to both EBV-type reference genomes (EBV1 and EBV2) using BWA and SAMtools. We constructed VCF files with VCFtools and used the information contained in these files to predict EBV type. Type classification was based on coverage, mapped reads and number of variants considering EBNA2 and the entire EBNA3 gene family. All together 194 samples were classificated as EBV1, 20 samples were EBV2, 4 were recombinant. Regarding Argentinean isolates, 9 were EBV1 and 6 EBV2. EBV1 sequences were further studied given their greater worldwide prevalence. In the phylogenetic tree no geographical structure was detected, except for the Asian sequences. Argentinian isolates segregated together with African and European isolates, whereas only three genomes clustered with Asian clades. Asian isolates presented more variants when compared to the reference and, lesser genetic diversity amongst isolates from other geographical regions. Geographical separation of Asiatic sequences was confirmed by PCA.Conclusions: EBV2 resulted more prevalent than previously described. We expanded data on EBV complete genomes from Argentina and inferred a closer phylogenetic relation with Africa and Europe; a fact that may be influenced by the introduction of African slaves during European colonization. Possible virus introduction routes based on phylogeographic analysis of dated sequences and considering the migration history of our country will be performed.