P20

The Epstein–Barr virus (EBV) represents an etiological agent for a number of human benign and malignant tumors. One of the EBV encoded proteins, the latent membrane protein 1 (LMP1), is involved in activation of many signaling pathways and transcription factors leading EBV infected cells to immortalization and transformation. It’s well known that almost all worlds’ population is infected with EBV. As usually, infection occurs during early childhood without serious consequences for infected people. At the same time a secondary infection by additional EBV strain(s) occurs quite often. During the in vitro cultivation of peripheral blood lymphocyte from persons infected with multiple strains of the virus, only one of them having LMP1 oncogene with highest transforming potential becomes dominant while the others are eliminated. To figure out whether pattern of LMP1 expressions reflects the origin of EBV strains, six cell lines from patients with tumors, associated and not-associated with the virus and healthy individuals were established. The nucleotide and deductive amino acid (a.a.) sequences of LMP1 isolates tested were analyzed and compared with those of LMP1 isolates obtained from eight cell lines of African and Japanese EBV-associated Burkitt’s lymphomas (BL) origin. As the result, in four out of six cell lines of Russian origin (2 from patients with lymphoid pathology and 2 from PBLs of blood donors) the low divergent LMP1 B95.8/A variant characterized by a low transforming activity and a small number of a.a. substitutions was detected. For other two cell lines originated from EBV-associated patient with nasopharyngeal carcinoma and not virus-associated Hodgkin’s lymphoma patient the LMP1Med- and LMP1China1 variants, characterized by a larger set of mutations and high transforming potential, were found. Low divergent LMP1 variants (B95.8 or B95.8/A) were observed for 13 of 15 LMP1 samples from PBLs of Russian blood donors; in 2 donors highly divergent China1 and NC LMP1 variants were also detected. Among eight cell lines of BL origin three lines were the sources of the prototype EBV strain B95.8 (Jijoye, P3HR1, Raji). From other five cell lines (Daudi, Namalva, Ag 876, NC37 and Akata) LMP1 variants Med- and China1, characterized by a significant number of mutations and high transforming capacity were obtained. Genetic relationship between LMP1 isolates from cell lines of Russian and BL origin were analyzed by the phylogenetic tree. It follows from the constructed tree that cell lines of Russian and BL lymphoma origin formed two separate clusters located at the tree a distance from each other, indicating genetic proximity for respective groups of cell lines. The data obtained complemented with the results of our previous studies suggest that among Russians represented by cancer patients and healthy individuals, EBV strains with predominantly low transforming capacity of LMP1 are persisting. These findings are likely can explain the non-endemic nature of the EBV-associated pathologies in Russia.On the other hand, one can speculate that in African countries which are endemic for BL highly oncogenic strains of EBV are dominated, the indirect confirmation of what is the detection in cell lines of BL origin LMP1 isolates having high transforming activity. The results of this study let us also to suggest that LMP1 expression pattern in non-endemic region like Russia does not reflect the type of malignancy but rather reflect their geographic origin