[Epstein-Barr virus (Herpesviridae: Lymphocryptovirus) types 1 and 2 and other viral markers in patients with nasopharyngeal carcinoma in two geographically and ethnically distinct regions of Russia].

INTRODUCTION: The discovery of two types of Epstein-Barr virus (EBV) (EBV-1 and EBV-2) that have different biological properties stimulated the search for neoplasms associated with each type of the virus. The aim of the work is to study the nature of the association of nasopharyngeal cancer (NPC) with EBV-1 and EBV-2, serological activity for each viral type and the concentration of EBV DNA in the blood plasma of two gender, age and ethnic groups of NPC patients that represent geographically and climatically different regions of Russia,. MATERIALS AND METHODS: In the blood plasma of patients with NPC and other non- EBV associated tumors of oral cavity (OTOCEBV-) from the North Caucasian (NCFD) and Central (CFD) Federal Districts of Russia, the types of EBV and the concentration of viral DNA were determined using respectively «nested¼ and real time PCR; titers of IgG and IgA antibodies to viral capsid antigen (VCA) were measured in indirect immunofluorescence assay. RESULTS: The blood plasma samples testing showed that NPC and OTOCEBV- patients were infected with both types of EBV in approximately equal proportions. In two groups of NPC patients infected with one of the virus types only, EBV-1 or EBV-2, respectively, no statistically significant differences were found between the geometric mean values of IgG and IgA anti-EBV antibody titers and viral DNA concentrations in blood plasma. The distribution of virus types was not affected by either patient gender or ethnogeographic origin. The difference was found only between age groups: EBV-2 dominated in NPC patients up to 60 years, and EBV-1 was prevalent in patients over 60 years. CONCLUSION: The lack of the predominance of one of EBV types in NPC patients that are the representatives of different ethnic groups from geographically and climatically different regions, suggests that none of these factors play an important role in the NPC carcinogenesis. Evidently, each type of EBV, EBV-1 or EBV-2, if the necessary conditions arise, are able to exhibit its oncogenic potential to initiate tumor development.

[Epstein-Barr virus (Herpesviridae: Gammaherpesvirinae: Lymphocryptovirus: Human gammaherpesvirus 4) in Kalmyks and Slavs living in Russia: virus types, LMP1 oncogene variants, and malignancies].

INTRODUCTION: The discovery of the Epstein-Barr virus types (Herpesviridae: Gammaherpesvirinae: Lymphocryptovirus: Human gammaherpesvirus 4) (EBV) - EBV-1 and EBV-2, which have different transforming abilities in vitro, stimulated the study of their prevalence in populations in order to elucidate the relationship with malignant neoplasms.The aims of the work are to study the prevalence of EBV-1 and EBV-2 among representatives of 2 ethnic groups of Russia, Kalmyks and Slavs, sequencing analysis of the LMP1 oncogene in virus isolates, and analysis of the correlation between virus types and the incidence of certain forms of tumors. MATERIALS AND METHODS: DNA samples were isolated from the biological material of oral swabs obtained from ethnic Kalmyks of the Republic of Kalmykia (RK) (n = 50) and Slavs, residents of the Moscow Region (MR) (n = 40). DNA samples were used to amplify EBV DNA, followed by determination of its concentration per 1 cell of washout, amplification of the LMP1 oncogene in viral samples, their sequencing, and determination of LMP1 protein variants. RESULTS: It has been established that with the same burden of EBV among representatives of both ethnic groups in the Kalmyk group, the ratio of persons infected with transforming and non-transforming types of the virus was almost the same (EBV-1 - 51%; and EBV-2 - 49%). Meanwhile, in the group of Slavs the transforming EBV-1 type virus dominated (80.6%). The predominance of EBV-1 type in representatives of the Slavs correlated with increased incidence of certain forms of tumors in the population of the MR when compared with similar values in the population of the RK, where both types of the virus were prevalent. Differences between the compared rates of cancer incidence were not statistically significant. Analysis of viral isolates showed a similar set of LMP1 variants in both ethnic groups. CONCLUSION: In order to establish the influence of EBV types on the incidence of malignant tumors, additional studies involving representatives of various ethnic groups from different geographical regions are needed.

[Ancient variants of the Epstein-Barr virus (Herpesviridae, Lymphocryptovirus, HHV-4): hypotheses and facts.]

INTRODUCTION: Molecular studies have shown that viruses appeared in the early stages of the evolution of life. For millions of years, viruses have evolved by changing old and acquiring new sequences in their RNA or DNA. It is assumed that most viruses have common ancestors. Such an ancestor, an ancient strain, probably existed for Epstein-Barr virus (EBV) as well. AIM: To find out whether ancient strains of EBV persist in modern Russian ethnic groups today. MATERIAL AND METHODS: The object of the study was the EBV LMP1oncogene, which is most suitable for molecular genetic analysis. LMP1 was amplified from the oral cavity washings obtained from representatives of two ancient ethnic groups of Russia - Tatars and Slavs. The LMP1 amplicons were sequenced in both directions; their nucleotide sequences translated into amino acid (LMP1) were evaluated using the classification suggested by Edwards et al. 1999. To establish genetic relationships between LMP1 variants, a phylogenetic tree was constructed by the neighbor-joining method using the MEGA software package. RESULTS AND DISCUSSION: Analysis of LMP1 sequences from washings of the Slavs oral cavity demonstrated the presence of LMP1 variants with varying degrees of transforming potential: B98.5/A, China1, Med-, and NC. The analysis of LMP1 sequences from washings of Tatar oral cavity also made it possible to identify oncoprotein variants such as B95.8/A, China1, Med-, as well as a group of variants out of classifications (LMP1-OK). An important finding was the identification of 7 variants of LMP1 from Tatars, designated as LMP1-TatK, that contained two unique deletions of 5 aa in codons 312-316 and 382-386, which were absent in the LMP1 variants from Slavs and from previously examined cancer patients and healthy individuals, as well as in sequences from open computer databases. The uniqueness of the LMP1-TatK variant is confirmed both by phylogenetic analysis of LMP1 sequences of Tatar origin and by the analysis of 11 aa repeats and 5 aa insertions in the C-terminal region of the oncoprotein. The morbidity and mortality rates from neoplasms, including EBV-associated pathologies, did not differ significantly between two studied ethnic groups infected with different EBV strains. CONCLUSION: The data obtained allowed us to suggest that: 1) LMP1-TatK could be refered to an evolutionarily ancient EBV strain that persists among Tatars and; 2) LMP1-TatK belongs to the so-called "Volga" EBV virus strain, the common strain among the population of the Volga region. Extended studies of EBV isolates from residents of this region may probably shed the light on the origin of LMP1-TatK.