Coevolution of Sites under Immune Selection Shapes Epstein-Barr Virus Population Structure.

Fanny Wegner,Florent Lassalle,François Balloux,Daniel P Depledge,Judith Breuer

doi:10.1093/molbev/msz152

Fanny Wegner, Florent Lassalle + Show 3 more

Open Access

https://doi.org/10.1093/molbev/msz152

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Abstract

Epstein–Barr virus (EBV) is one of the most common viral infections in humans and persists within its host for life. EBV therefore represents an extremely successful virus that has evolved complex strategies to evade the host’s innate and adaptive immune response during both initial and persistent stages of infection. Here, we conducted a comparative genomics analysis on 223 whole genome sequences of worldwide EBV strains. We recover extensive genome-wide linkage disequilibrium (LD) despite pervasive genetic recombination. This pattern is explained by the global EBV population being subdivided into three main subpopulations, one primarily found in East Asia, one in Southeast Asia and Oceania, and the third including most of the other globally distributed genomes we analyzed. Additionally, sites in LD were overrepresented in immunogenic genes. Taken together, our results suggest that host immune selection and local adaptation to different human host populations has shaped the genome-wide patterns of genetic diversity in EBV.

Highlights

Epstein-Barr virus (EBV) is a member of the gamma-herpesviruses family, present in most humans worldwide
EBV has been associated with a variety of cancerous diseases of B cell origin, such as endemic Burkitt’s lymphoma (BL), Hodgkin’s lymphoma (HL) and post-transplant lymphoproliferative disorder (PTLD), cancers of epithelial origin including nasopharyngeal carcinoma (NPC) and gastric carcinoma and even in rare cases NK- and T-cell tumours (Young et al 2016)
Development of disease is associated with various factors, such as immune status (e.g. PTLD, HIV-related lymphoma), co-infections and geography with EBV-positive NPC prevalent in adults from Southern China and Northern Africa, and endemic BL in children from equatorial Africa

Summary

Introduction

Epstein-Barr virus (EBV) is a member of the gamma-herpesviruses family, present in most humans worldwide. The double-stranded DNA genome of EBV has a length of around 172 kb and contains at least 94 annotated open reading frames (ORF). It usually resides as a circular, doublestranded DNA molecule in the nucleus. Palser et al (2015) reported two cases of inter-typic recombinants, and presented evidence for multiple recombination events throughout the genome. This latter observation crucially impacts how EBV ancestry can be studied as recombination events are expected to affect tree topology and can render inference derived from phylogenetic approaches largely meaningless (Rieux and Balloux 2016)

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