EPSTEIN–BARR VIRUS IN THE POPULATION OF TWO GEOGRAPHICALLY DIFFERENT REGIONS OF RUSSIA

Abstract

It is well known that the Epstein–Barr virus (EBV) being widely spread in the human population is also the etiologic agent for a number of malignancies. A notable feature of tumors associated with EBV is their different incidence in various geographical regions, that, as suggested, related with mutational events in multiple loci of the EBV genome and its oncogene, the latent membrane protein 1 (LMP1), associated with the transforming potential of the virus. Given the multi-ethnic composition of Russian population and the diversity of geographical areas and conditions of their residence, it was relevant to examine the representatives of different geographical regions for the nature of their relationship with EBV. To solve this task the antibody response to locally circulating EBV strains, determined by indirect immunofluorescence, was studied in residents of the Central, North Caucasus and Far Eastern Federal Districts, represented by healthy individuals and patients with various head and neck tumors. The levels of antibody titers obtained were compared with the incidence rates of nasopharyngeal tumors (NPT) in population of above Districts. In order to determine possible structural modifications in LMP1 gene of EBV strains persisting in selected geographic regions, samples of the gene have been amplified from a biological material collected by “nested” PCR and sequenced. The results obtained have shown that levels of antibody response to EBV among representatives of the regions included in the study vary significantly. It was found that in residents of the Dagestan and the Chechen Republics, the inhabitants of the North Caucasus Federal District, the correlation between enhanced humoral response to EBV and increased incidence of NPT was detected. Since among NPT the EBV-associated form of nasopharyngeal carcinoma (NPCEBV) is dominated, the findings allow us to suggest that the population of these Republics have genetic predisposition to increased EBV replication and, consequently, an elevated incidence of NPCEBV. The study also showed that representatives of the regions tested are infected with EBV strains, LMP1 variants of which such as B95.8, China 1, Med+, Med– and NC, are known in the literature. However, LMP1 variant, specifically associated with NPCEBV, has not been identified. This study showed for the first time the genetic heterogeneity of EBV strains circulating among population of different geographical regions of the country, and the existence of correlation between antibody response to EBV and the incidence of nasopharyngeal tumors, including NPCEBV.

Keywords

• epstein–barr virus
• antibody response
• nasopharyngeal cancer
• lmp1 oncogene