Phylodynamic characteristics of the LMP-1 gene of the Epstein–Barr virus isolated in the Nizhny Novgorod region

Abstract

Introduction. Epstein–Barr virus (EBV) is one of the most common herpesviruses and has a pronounced genetic polymorphism. The study of the phylodynamic characteristics of the virus is an important aspect of the study of evolutionary changes in the LMP-1 gene and their consequences. The aim of the work was a philodynamic analysis of EBV isolates from Nizhny Novgorod region based on the C-terminal fragment of the LMP-1 gene. Materials and methods. The study included 158 EBV isolates obtained from blood leukocytes and saliva of children aged 1–17 years with a diagnosis of infectious mononucleosis caused by EBV (n = 68) and apparently healthy children of comparable sex and age (n = 29). LMP-1 genovariants were obtained using the Sanger sequencing method. Comparative analysis of amino acid sequences was performed using the MEGA X program. Philodynamic analysis of the obtained nucleotide sequences and isolates deposited in GenBank was carried out using the BEAST v. 1.10.4 software package. Recombination analysis was performed using the Simplot program. Results. 158 nucleotide sequences of the C-terminal fragment of the LMP-1 gene from Nizhny Novgorod region EBV isolates were obtained and deposited in the GenBank database. The circulation time of the nearest common ancestor for the modified B95-8 genovariants with G212S + E328Q + S366T and NC mutations with the D250N substitution has been established dating back to 1994 and 1923. The rate of evolution of these genovariants was the highest and amounted to 1.298 × 10–4 and 7.868 × 10–4 nucleotide substitutions/site/year. Recombinations were detected in the Nizhny Novgorod region sequences Med-, B95-8, China 1 with mutations G212S, G212S, E214Q, respectively. Conclusion. For the first time, a phylodynamic characterization of Nizhny Novgorod region isolates and LMP-1 EBV genovariants isolated in various regions of the world is given. The data obtained expand the existing understanding of the circulation of EBV LMP-1 genovariants in the territory of the European part of Russia.