The molecular epidemiology and evolution of Epstein-Barr virus: Sequence variation and genetic recombination in the latent membrane protein-1 gene

The phylogeny and evolution of Epstein-Barr virus (EBV) genetic variation a re poorly understood. EBV latent membrane protein-1 (LMP-1) gene sequences are especially heterogeneous and may be useful as a tool for EBV genotype i dentification. Therefore, LMP-1 sequences obtained directly from EBV-infect ed human tissues were examined by PCR amplification and cloning. EBV genoty pes were defined as "strains" from among 22 identified LMP-1 sequence patte rns. Three molecular mechanisms were identified by which genetic diversity arises in the LMP-1 gene: point mutation, sequence deletion or duplication, and homologous recombination, The rate of LMP-1 gene evolution was found t o be accelerated by coinfection with multiple EBV strains. The results of t his study refine our understanding of LMP-1 sequence variation and enable a ccurate discrimination between independent EBV infection events and the con sequence of intrahost EBV evolution. Thus, this LMP-1 sequence-based approa ch to EBV molecular epidemiology will facilitate the study of intrahost EBV infection, coinfection, and persistence.