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This paper reports the analysis of the nucleotide sequences of the 5'-untranslated region (5'-UTR) of tick-borne encephalitis virus (TBEV) genomic RNA isolated from 39 individual taiga ticks collected in several regions of Northern Eurasia. The sequences of 5'-UTRs of the Siberian and Far East TBEV genotypes were 89% and 95% identical to the prototype strains (Zausaev and 205), respectively. The detected nucleotide substitutions were typical for these two TBEV genotypes, which made possible unambiguous identification. Both conservative and variable motifs were detected in the 5'-UTR RNA. The B2, C1, and C2 elements of the Y-shaped 5'-UTR structure and the presumable viral RNA-dependent RNA-polymerase binding site were the most variable. The A2, CS A, CS B elements as well as the start codon were conservative. Interestingly, five substitutions in the 5'-UTR C1 variable element of the TBEVs isolated in different geographical regions were strictly conservative, while 11 different substitutions were detected in this element among the laboratory TBEV variants. A little less that a third of all nucleotide substitutions were mapped outside the main elements of the Y-shaped structure. In general, nucleotide substitutions were localized to stem structures, not being found in the hairpin regions of the TBEV 5'-UTR. The results indicated significant variability of the genomic RNA 5'-UTR in the TBEV laboratory strains and field isolates obtained from different geographical regions. It has been suggested that genetic variability of 5'-UTR is characteristic of the TBEV genome 5'-UTR organization and may serve as a structural basis for virus efficient replication in various avian, mammalian, and ixodic tick cells.

The C11-13 strain from the Siberian subtype of tick-borne encephalitis virus (TBEV) was isolated from human brain using pig embryo kidney (PEK), 293, and Neuro-2a cells. Analysis of the complete viral genome of the C11-13 variants during six passages in these cells revealed that the cell-adapted C11-13 variants had multiple amino acid substitutions as compared to TBEV from human brain. Seven out of eight amino acids substitutions in the high-replicating C11-13(PEK) variant mapped to non-structural proteins; 13 out of 14 substitutions in the well-replicating C11-13(293) variant, and all four substitutions in the low-replicating C11-13(Neuro-2a) variant were also localized in non-structural proteins, predominantly in the NS2a (2), NS3 (6) and NS5 (3) proteins. The substitutions NS2a (Asn → Asp), NS2a(Leu → Val) in the N-terminus of NS2a and NS3(His → Gln) in the helicase domain of NS3 were found in all selected variants. We postulate that multiple substitutions in the NS2a, NS3 and NS5 genes play a key role in adaptation of TBEV to different cells.

Резюме. Большинство сведений об интимных механизмах пожизненной персистенции Heliсobacter pylori (НР) в слизистой оболочке желудка и резистентности к данной инфекции базируются только на феноме нологических данных, например на отсутствии заболевания или низкой колонизации мышей и людей, спон танно синтезирующих высокие концентрации IL 2. 108 пациентов, страдающих НР ассоциированной ЯБЖ, были разделены на две группы. Пациенты I группы получали стандартную терапию, включающую два ан тибиотика, ингибиторы протонной помпы и Н 2 блокаторы. Больных II группы лечили аналогично, но вме сто антибиотиков они получали 0,1 мг rIL 2-Ронколейкина, растворенного в 2 мл 0,9% NaCl через гаст роскоп в 4 6 точек субмукозно параульцерально и одновременно 0,4 мг в/в согласно инструкции. Процеду ру повторяли трижды с интервалом 72 часа. Результатом иммунотерапии явилось повышение концентра ции CD25 + , HLA DR + CD16 + CD56 + лимфоцитов в крови, сывороточной концентрации IL 1α в 3 раза, IL 6-в 4 раза и IFNγ более чем в 20 раз при стимуляции бактерицидной активности нейтрофильных грануло цитов. Эрадикация НР была достигнута у 95,4% пациентов против 81,5% в контроле, период заживления язвы составил 10,79±0,46 дней, а в группе, получавшей традиционную терапию 35,23±1,58 дней.

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