vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ20.597vavilov-2482Research ArticleМОЛЕКУЛЯРНАЯ И КЛЕТОЧНАЯ БИОЛОГИЯMOLECULAR AND CELL BIOLOGYХарактеристика полногеномной последовательности рекомбинантного норовируса генотипа GILP16/GIL4_Sydney_2012, выявленного в РоссииCharacterization of the complete genome sequence of the recombinant norovirus GII.P16/GII.4_Sydney_2012 revealed in Russiahttps://orcid.org/0000-0001-6787-8393ЖираковскаяЕ. В.ZhirakovskaiaE. V.

Новосибирск

Novosibirsk

https://orcid.org/0000-0001-5613-5447ТикуновА. Ю.TikunovA. Y.

Новосибирск

СоколовС. Н.SokolovS. N.

Новосибирск; Р. п. Кольцово, Новосибирская область

Koltsovo, Novosibirsk region

КравчукБ. И.KravchukB. I.

Новосибирск

https://orcid.org/0000-0003-2625-5442КрасноваЕ. И.KrasnovaE. I.https://orcid.org/0000-0002-1687-8278ТикуноваН. В.TikunovaN. V.

Новосибирск

tikunova@niboch.nsc.ruИнститут химической биологии и фундаментальной медицины, Сибирское отделение Российской академии наукРоссияInstitute of diemical Biology аnd Fundamental Medicine, Siberian Branch of the Russian Academy of SciencesRussian FederationИнститут химической биологии и фундаментальной медицины, Сибирское отделение Российской академии наук; Государственный научный центр вирусологии и биотехнологии «Вектор»РоссияInstitute of diemical Biology аnd Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences; State Research Center of Virology and Biotechnology VectorRussian FederationНовосибирский государственный медицинский университет Минздрава РоссииРоссияNovosibirsk State Medical University, Department of Infectious DiseasesRussian Federation2020180320202416979Copyright © Жираковская Е.В., Тикунов А.Ю., Соколов С.Н., Кравчук Б.И., Краснова Е.И., Тикунова Н.В., 20202020Жираковская Е.В., Тикунов А.Ю., Соколов С.Н., Кравчук Б.И., Краснова Е.И., Тикунова Н.В.Zhirakovskaia E.V., Tikunov A.Y., Sokolov S.N., Kravchuk B.I., Krasnova E.I., Tikunova N.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/2482

Норовирусы (сем. Caliciviridae) считаются частой причиной острого гастроэнтерита у людей всех возрастов. Эти небольшие безоболочечные вирусы с одноцепочечным (+)РНК-геномом характеризуются высокой генетической вариабельностью. По всему миру наблюдается постоянное изменение генетического разнообразия циркулирующих норовирусов и появление новых рекомбинантных вариантов. Недавно опубликованы данные о распространении рекомбинантных штаммов норовируса, в которых новая полимераза генотипа GII.P16 сочеталась с капсидными белками VP1 разных генотипов. В рамках мониторинга спорадических случаев острых гастроэнтеритов в Новосибирске в 2016 г. было протестировано 46 клинических образцов от детей с диареей. Методом ОТ-ПЦР норовирус детектирован в шести клинических образцах от госпитализированных детей. Выявленные норовирусы путем секвенирования региона перекрывания ORF1/ORF2 были классифицированы как рекомбинантные варианты GII.P21/GII.3, GII.Pe/GII.4_Sydney_2012 и GII.P16/GII.4_Sydney_2012. Появление нового рекомбинантного генотипа GII.P16/GII.4_Sydney_2012 впервые зафиксировано в Новосибирске весной 2016 г. До этого исследования в базе данных GenBank было доступно всего четыре полногеномные последовательности российских штаммов норовируса генотипа GII.P16/GII.3. В настоящей работе была определена полная последовательность генома российского штамма Hu/GII.P16-GII.4/RUS/Novosibirsk/NS16-C38/2016 (GenBankKY210980). Сравнение нуклеотидной и выведенной аминокислотной последовательностей показало высокую гомологию этого российского штамма со штаммами генотипа GII.P16/GII.4_Sydney_2012 из других регионов мира. Сравнительный анализ показал, что уникальные замены произошли в последовательностях генов полимеразы генотипа GII.P16, N-терминального белка p48 и минорного капсидного белка VP2, при этом существенных изменений в гене основного капсидного белка VP1 не наблюдалось. Анализ функциональной значимости этих изменений позволил предположить, что широкое распространение штаммов с новой полимеразой GII.P16, возможно, связано как с несколькими аминокислотными заменами в активном центре полимеразы, так и со вставкой остатка глутаминовой кислоты или глицина в N-терминальном белке p48, который блокирует секреторный иммунитет эпителиальных клеток кишечника. Дальнейший мониторинг генотипов позволит оценить распространение рекомбинантных норовирусов с полимеразой GII.P16 на территории России.

Noroviruses (the Caliciviridae family) are a common cause of acute gastroenteritis in all age groups. These small non-envelope viruses with a single-stranded (+)RNA genome are characterized by high genetic variability. Continuous changes in the genetic diversity of co-circulating noroviruses and the emergence of new recombinant variants are observed worldwide. Recently, new recombinant noroviruses with a novel GII.P16 polymerase associated with different capsid proteins VP1 were reported. As a part of the surveillance study of sporadic cases of acute gastroenteritis in Novosibirsk, a total of 46 clinical samples from children with diarrhea were screened in 2016. Norovirus was detected in six samples from hospitalized children by RT-PCR. The identified noroviruses were classified as recombinant variants GII.P21/GII.3, GII.Pe/GII.4_Sydney_2012, and GII.P16/GII.4_Sydney_2012 by sequencing of the ORF1/ORF2 junction. In Novosibirsk, the first appearance of the new recombinant genotype GII.P16/GII.4_Sydney_2012 was recorded in spring 2016. Before this study, only four complete genome sequences of the Russian GII.P16/GII.3 norovirus strains were available in the GenBank database. In this work, the complete genome sequence of the Russian strain Hu/GII.P16-GII.4/RUS/Novosibirsk/NS16-C38/2016 (GenBank KY210980) was determined. A comparison of the nucleotide and the deduced amino acid sequences showed a high homology of the Russian strain with GII.P16/GII.4_Sydney_2012 strains from other parts of the world. A comparative analysis showed that several unique substitutions occurred in the GII.P16 polymerase, N-terminal p48 protein, and minor capsid protein VP2 genes, while no unique changes in the capsid VP1 gene were observed. A functional significance of these changes suggests that a wide distribution of the strains with the novel GII.P16 polymerase may be associated both with several amino acid substitutions in the polymerase active center and with the insertion of glutamic acid or glycine in an N-terminal p48 protein that blocks the secretory immunity of intestinal epithelial cells. Further monitoring of genotypes will allow determining the distribution of norovirus recombinants with the polymerase GII.P16 in Russia.

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The authors declare that there are no conflicts of interest present.