Epstein-Barr Virus Sequence Variation—Biology and Disease

Abstract

Some key questions in Epstein-Barr virus (EBV) biology center on whether naturally occurring sequence differences in the virus affect infection or EBV associated diseases. Understanding the pattern of EBV sequence variation is also important for possible development of EBV vaccines. At present EBV isolates worldwide can be grouped into Type 1 and Type 2, a classification based on the EBNA2 gene sequence. Type 1 EBV is the most prevalent worldwide but Type 2 is common in parts of Africa. Type 1 transforms human B cells into lymphoblastoid cell lines much more efficiently than Type 2 EBV. Molecular mechanisms that may account for this difference in cell transformation are now becoming clearer. Advances in sequencing technology will greatly increase the amount of whole EBV genome data for EBV isolated from different parts of the world. Study of regional variation of EBV strains independent of the Type 1/Type 2 classification and systematic investigation of the relationship between viral strains, infection and disease will become possible. The recent discovery that specific mutation of the EBV EBNA3B gene may be linked to development of diffuse large B cell lymphoma illustrates the importance that mutations in the virus genome may have in infection and human disease.

A Single Amino Acid in EBNA-2 Determines Superior B Lymphoblastoid Cell Line Growth Maintenance by Epstein-Barr Virus Type 1 EBNA-2

“…Mutations in the EBNA-3B gene linked to diffuse large B cell lymphoma also support the idea that variation in EBV sequence may be linked to human disease (2). Type 1 and type 2 strains are the main natural functional variation known in Epstein-Barr virus (3,4). The types are defined by sequence differences in the EBNA-2 gene, but there are also linked sequence changes in the EBNA-3 family of genes (3).…”

Geographic Population Structure in Epstein-Barr Virus Revealed by Comparative Genomics

“…Patterns of genetic divergence of the EBNA2 and EBNA3a,b,c alleles allow the division of EBV isolates into types 1 and 2 that have differing geographical distributions, with the latter more widespread in Africa. Single locus genotyping studies have also tentatively associated specific variants with particular clinical manifestations and/or geographic regions (reviewed in Tzellos and Farrell 2012). However, EBV is subject to recombination (Walling and Raab-Traub 1994) which complicates such assignments, and comparisons of complete genome sequences suggest that recombination is widespread (McGeoch and Gatherer 2007; Palser et al 2015).…”

Epstein–Barr Virus Strain Variation

“…In general, we need to know what is wild-type EBV. This chapter integrates and updates some previously published reviews on EBV sequence variation (Jenkins and Farrell 1996;Tzellos and Farrell 2012).…”