Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1788410.15789/2220-7619-IRT-17884REVIEWSОБЗОРЫReview ArticleImmune response to norovirus infectionИммунный ответ на норовирусную инфекциюhttps://orcid.org/0000-0003-1993-06225958-4703TalayevVladimir Y.ТалаевВладимир Юрьевич
Russian Federation

DSc (Medicine), Professor, Head of the Laboratory of Cellular Immunology

д.м.н., профессор, зав. лабораторией клеточной иммунологии

talaev@inbox.ruhttps://orcid.org/0000-0003-4527-61349438-9974BabaykinaO. N.БабайкинаО. Н.
Russian Federation

PhD (Medicine), Senior Researcher, Laboratory of Cellular Immunology

к.м.н., старший научный сотрудник лаборатории клеточной иммунологии

olga_babaykina@inbox.ruhttps://orcid.org/0000-0003-1801-96936615-7674KurkovaE. V.КурковаЕ. В.
Russian Federation

PhD (Biology), Senior Researcher, Laboratory of Cellular Immunology

к.б.н., старший научный сотрудник лаборатории клеточной иммунологии

el2v@mail.ruhttps://orcid.org/0009-0004-5213-11576710-2294ZharovaA.-M. D.ЖароваА.-М. Д.
Russian Federation

Assistant Professor, Department of General and Medical Genetics, Institute of Biology and Biomedicine

ассистент кафедры общей и медицинской генетики Института биологии и биомедицины

uglich_marie@mail.ruhttps://orcid.org/0000-0003-4097-67808340-7583SvetlovaM. V.СветловаМ. В.
Russian Federation

PhD (Biology), Senior Researcher, Laboratory of Cellular Immunology

к.б.н., старший научный сотрудник лаборатории клеточной иммунологии

marya.talaeva@yandex.ruhttps://orcid.org/0000-0001-5063-311185471698003522-4289ZaichenkoI. Y.ЗаиченкоИ. Е.
Russian Federation

PhD (Biology), Leading Researcher, Laboratory of Cellular Immunology

к.б.н., ведущий научный сотрудник лаборатории клеточной иммунологии

imm.irina@mail.ruAcademician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology of Russian Federal Consumer Rights Protection and Human Health Control ServiceФБУН Нижегородский научно-исследовательский институт эпидемиологии и микробиологии им. академика И.Н.Блохиной РоспотребнадзораNational Research Lobachevsky State UniversityНижегородский государственный университет им. Н.И. Лобачевского01082025081220251558098250603202526072025Copyright ©; 2025, Talayev V.Y., Babaykina O.N., Kurkova E.V., Zharova A.D., Svetlova M.V., Zaichenko I.Y.Copyright ©; 2025, Талаев В.Ю., Бабайкина О.Н., Куркова Е.В., Жарова А.Д., Светлова М.В., Заиченко И.Е.2025Talayev V.Y., Babaykina O.N., Kurkova E.V., Zharova A.D., Svetlova M.V., Zaichenko I.Y.Талаев В.Ю., Бабайкина О.Н., Куркова Е.В., Жарова А.Д., Светлова М.В., Заиченко И.Е.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/17884

Noroviruses are non-enveloped viruses of the family Caliciviridae. The norovirus variants that infect humans are highly contagious and are a leading cause of outbreaks for nonbacterial gastroenteritis. In the etiological pattern of acute viral intestinal infections, noroviruses hold the second place after rotaviruses. In countries with widespread use of rotavirus vaccines, the incidence of rotavirus infection has declined, whereas noroviruses have become the leading cause of nonbacterial gastroenteritis. A further decline in the incidence of intestinal infections can be achieved by using a vaccine against norovirus, however work on developing this vaccine is still underway. This review provides information on the circulation of genetic norovirus variants, its antigenic epitopes from structural and non-structural proteins, specific immune response, the regulatory activity of viral proteins, and formation of individual and collective immunity against noroviruses. The presented data indicate that immunity generated by norovirus infection has a limited duration and is apparently restricted by the norovirus genotype. The narrow specificity of immunity and the high level of genetic virus variation complicate targeted vaccine development. The long-term and very active circulation of noroviruses of the gene variant GII.4 Sydney 2012 suggests that it has properties that prevent the specific immunity formation in human population. Identification of such properties may be important for developing effective vaccine. Evaluating the protective significance of the immune response to the VP2 protein and virus’s non-structural proteins is also of considerable interest. Until these questions are solved, the most obvious candidates for the norovirus vaccine are capsid proteins VP1 of the gene variant GII.4 Sydney 2012, as well as other most relevant virus variants. Currently circulating strains of the GII.17 genotype exemplify such relevant variants. It also seems likely that, if the vaccine is successfully designed, periodic modification of its antigenic composition will be required in accordance with the epidemiological situation.

Норовирусы являются безоболочечными вирусами из семейства Caliciviridae. Часть норовирусов вызывает острый гастроэнтерит у людей. Эти норовирусы обладают высокой контагиозностью и являются основной причиной вспышек небактериальных гастроэнтеритов, а в общей структуре острых вирусных кишечных инфекций занимают второе место после ротавирусов. В странах с массовым применением вакцин против ротавирусов заболеваемость ротавирусной инфекцией снизилась, в результате чего норовирусы оказались на первом месте в этиологической структуре небактериальных гастроэнтеритов. Очевидно, что дальнейшее снижение заболеваемости кишечными инфекциями может быть достигнуто с помощью внедрения вакцинопрофилактики норовирусной инфекции, однако работы по созданию норовирусной вакцины пока не привели к желаемому результату. В данном обзоре приведены сведения о циркуляции генетических вариантов норовирусов, антигенных эпитопах главного и минорного структурных белков, а также неструктурных белков норовирусов, об иммунном ответе на норовирусные антигены, о регуляторной активности вирусных белков и о формировании индивидуального и популяционного иммунитета против норовирусов. Приведенные данные свидетельствуют о том, что при норовирусной инфекции формируется иммунитет с малым (по результатам экспериментов с заражением) или средним (по результатам эпидемиологического анализа) сроком защиты от норовируса. По-видимому, защитное действие постинфекционного иммунитета ограничено генотипом норовируса. Такая узкая специфичность иммунитета и большой уровень генетической вариации вируса усложняет разработку норовирусной вакцины. Необычно долгое циркулирование норовирусов геноварианта GII.4 Sydney 2012 наводит на мысль о существовании свойств, предотвращающих формирование невосприимчивости к этому варианту вируса в человеческой популяции. Выявление этих свойств может оказаться важным для разработки эффективной системы вакцинопрофилактики. Также существенный интерес представляет определение наличия или отсутствия защитной значимости иммунного ответа на белок VP2 и неструктурные белки вируса. До тех пор, пока не будут получены ответы на эти вопросы, наиболее очевидными кандидатами в состав норовирусной вакцины представляются капсидные белки VP1 геноварианта GII.4 Sydney 2012, а также других наиболее актуальных вариантов вируса. В настоящее время такими вариантами являются распространенные представители генотипа GII.17. Также представляется вероятным, что в случае успешного создания вакцины потребуется периодическая модификация ее антигенного состава в соответствии с эпидемиологической ситуацией.

immune responsenorovirusantigensevolutionary dynamicsimmune evasionantibodiesT cellsиммунный ответноровирусантигеныэволюционная динамикауклонение от иммунитетаантителаТ-клеткиЕпифанова Н.В., Луковникова Л.Б., Новикова Н.А., Парфенова О.В., Фомина С.Г. Эпидемические варианты норовирусов генотипа GII.4 в Нижнем Новгороде в 2006–2012 гг. // Журнал микробиологии, эпидемиологии и иммунобиологии. 2014. Т. 91, № 2. C. 64-72. [Epifanova N.V., Lukovnikova L.B., Novikova N.A., Parfenova O.V., Fomina S.G. Epidemic variants of norovirus genotype GII.4 in Nizhny Novgorod in 2006–2012. Zhurnal mikrobiologii, epidemiologii i immunobiologii = Journal of Microbiology, Epidemiology and Immunobiology, 2014, vol. 91, no. 2, pp. 64–72. (In Russ.)]Кожухова Е.А., Горбова И.В. Характеристика случаев острой диареи у взрослых больных с позитивной реакцией клинического материала на норовирус // Инфекция и иммунитет. 2019. Т. 9, № 2. С. 375–380. [Kozhukhova E.A., Gorbova I.V. Characteristics of acute diarrhea in adult patients positive for Norwalk virus. Infektsiya i immunitet = Russian Journal of Infection and Immunity, 2019, vol. 9, no. 2, pp. 375–380. (In Russ.)] doi: 10.15789/2220-7619-2019-2-375-380Aktepe T.E., Deerain J.M., Hyde J.L., Fritzlar S., Mead E.M., Carrera Montoya J., Hachani A., Pearson J.S., White P.A., Mackenzie J.M. Norovirus-mediated translation repression promotes macrophage cell death. PLoS Pathog., 2024, vol. 20, no. 9: e1012480. doi: 10.1371/journal.ppat.1012480Atmar R.L., Opekun A.R., Gilger M.A., Estes M.K., Crawford S.E., Neill F.H., Ramani S., Hill H., Ferreira J., Graham D.Y. Determination of the 50% human infectious dose for Norwalk virus. J. Infect. Dis., 2014, vol. 209, no. 7, pp. 1016–1022. doi: 10.1093/infdis/jit620Barclay L., Cannon J.L., Wikswo M.E., Phillips A.R., Browne H., Montmayeur A.M., Tatusov R.L., Burke R.M., Hall A.J., Vinjé J. Emerging novel GII.P16 noroviruses associated with multiple capsid genotypes. Viruses, 2019, vol. 11, no. 6: 535. doi: 10.3390/v11060535Baric R.S., Yount B., Lindesmith L., Harrington P.R., Greene S.R., Tseng F.C., Davis N., Johnston R.E., Klapper D.G., Moe C.L. Expression and self-assembly of norwalk virus capsid protein from venezuelan equine encephalitis virus replicons. J. Virol., 2002, vol. 76, no. 6, pp. 3023–3030. doi: 10.1128/jvi.76.6.3023-3030.2002Bartsch S.M., Lopman B.A., Ozawa S., Hall A.J., Lee B.Y. Global Economic Burden of Norovirus Gastroenteritis. PLoS One, 2016, vol. 11, no. 4: e0151219. doi: 10.1371/journal.pone.0151219Blacklow N.R., Cukor G., Bedigian M.K., Echeverria P., Greenberg H.B., Schreiber D.S., Trier J.S. Immune response and prevalence of antibody to Norwalk enteritis virus as determined by radioimmunoassay. J. Clin. Microbiol., 1979, vol. 10, no. 6, pp. 903–909. doi: 10.1128/jcm.10.6.903-909.1979Bok K., Abente E.J., Realpe-Quintero M., Mitra T., Sosnovtsev S.V., Kapikian A.Z., Green K.Y. Evolutionary dynamics of GII.4 noroviruses over a 34-year period. J. Virol., 2009, vol. 83, no. 22, pp. 11890–11901. doi: 10.1128/JVI.00864-09Bok K., Parra G.I., Mitra T., Abente E., Shaver C.K., Boon D., Engle R., Yu C., Kapikian A.Z., Sosnovtsev S.V., Purcell R.H., Green K.Y. Chimpanzees as an animal model for human norovirus infection and vaccine development. Proc. Natl. Acad. Sci. USA, 2011, vol. 108, pp. 325–330. doi: 10.1073/pnas.1014577107Boon D., Mahar J.E., Abente E.J., Kirkwood C.D., Purcell R.H., Kapikian A.Z., Green K.Y., Bok K. Comparative evolution of GII.3 and GII.4 norovirus over a 31-year period. J. Virol., 2011, vol. 85, no. 17, pp. 8656–8666. doi: 10.1128/JVI.00472-11Bull R.A., Hansman G.S., Clancy L.E., Tanaka M.M., Rawlinson W.D., White P.A. Norovirus recombination in ORF1/ORF2 overlap. Emerg. Infect. Dis., 2005, vol. 11, no. 7, pp. 1079–1085. doi: 10.3201/eid1107.041273Centers for Disease Control and Prevention (CDC). Emergence of new norovirus strain GII.4 Sydney–United States, 2012. MMWR Morb. Mortal. Wkly Rep., 2013, vol. 62, no. 3, p. 55.Chan M.C., Lee N., Hung T.N., Kwok K., Cheung K., Tin E.K.Y., Lai R.W.M., Nelson E.A.S., Leung T.F., Chan P.K.S. Rapid emergence and predominance of a broadly recognizing and fast-evolving norovirus GII.17 variant in late 2014. Nat. Commun., 2015, vol. 6: 10061. doi: 10.1038/ncomms10061Chan M.C.W., Hu Y., Chen H., Podkolzin A.T., Zaytseva E.V., Komano J., Sakon N., Poovorawan Y., Vongpunsawad S., Thanusuwannasak T., Hewitt J., Croucher D., Collins N., Vinjé J., Pang X.L., Lee B.E., de Graaf M., van Beek J., Vennema H., Koopmans M.P.G., Niendorf S., Poljsak-Prijatelj M., Steyer A., White P.A., Lun J.H., Mans J., Hung T.-N., Kwok K., Cheung K., Lee N., Chan P.K.S. Global spread of norovirus GII.17 Kawasaki 308, 2014–2016. Emerg. Infect. Dis., 2017, vol. 23, no. 8, pp. 1350–1354. doi: 10.3201/eid2308.161138Chen R., Neill J.D., Noel J.S., Hutson A.M., Glass R.I., Estes M.K., Prasad B.V. Inter- and intragenus structural variations in caliciviruses and their functional implications. J. Virol., 2004, vol. 78, no. 12, pp. 6469–6479. doi: 10.1128/JVI.78.12.6469-6479.2004Chhabra P., de Graaf M., Parra G.I., Chan M.C., Green K., Martella V., Wang Q., White P.A., Katayama K., Vennema H., Koopmans M.P.G., Vinjé J. Updated classification of norovirus genogroups and genotypes. J. Gen. Virol., 2019, vol. 100, no. 10, pp. 1393–1406. doi: 10.1099/jgv.0.001318Chhabra P., Wong S., Niendorf S., Lederer I., Vennema H., Faber M., Nisavanh A., Jacobsen S., Williams R., Colgan A., Yandle Z., Garvey P., Al-Hello H., Ambert-Balay K., Barclay L., de Graaf M., Celma C., Breuer J., Vinjé J., Douglas A. Increased circulation of GII.17 noroviruses, six European countries and the United States, 2023 to 2024. Euro Surveill., 2024, vol. 29, no. 39: 2400625. doi: 10.2807/1560-7917.ES.2024.29.39.2400625Conley M.J., McElwee M., Azmi L., Gabrielsen M., Byron O., Goodfellow I.G., Bhella D. Calicivirus VP2 forms a portal-like assembly following receptor engagement. Nature, 2019, vol. 565, no. 7739, pp. 377–381. doi: 10.1038/s41586-018-0852-1Costantini V.P., Cooper E.M., Hardaker H.L., Lee L.E., DeBess E.E., Cieslak P.R., Hall A.J., Vinjé J. Humoral and Mucosal Immune Responses to Human Norovirus in the Elderly. J. Infect. Dis., 2020, vol. 221, no. 11, pp. 1864–1874. doi: 10.1093/infdis/jiaa021Czako R., Atmar R.L., Opekun A.R., Gilger M.A., Graham D.Y., Estes M.K. Experimental human infection with Norwalk virus elicits a surrogate neutralizing antibody response with cross-genogroup activity. Clin. Vaccine Immunol., 2015, vol. 22, no. 2, pp. 221–228. doi: 10.1128/CVI.00516-14Dang W., Xu L., Yin Y., Chen S., Wang W., Hakim M.S., Chang K.O., Peppelenbosch M.P., Pan Q. IRF-1, RIG-I and MDA5 display potent antiviral activities against norovirus coordinately induced by different types of interferons. Antiviral Res., 2018, vol. 155, pp. 48–59. doi: 10.1016/j.antiviral.2018.05.004De Graaf M., van Beek J., Vennema H., Podkolzin A.T., Hewitt J., Bucardo F., Templeton K., Mans J., Nordgren J., Reuter G., Lynch M., Rasmussen L.D., Iritani N., Chan M.C., Martella V., Ambert-Balay K., Vinjé J., White P.A., Koopmans M.P. Emergence of a novel GII.17 norovirus — End of the GII.4 era? Euro Surveill., 2015, vol. 20, no. 26: 21178. doi: 10.2807/1560-7917.ES2015.20.26.21178De Graaf M., van Beek J., Koopmans M.P. Human norovirus transmission and evolution in a changing world. Nat. Rev. Microbiol., 2016, vol. 14, no. 7, pp. 421–433. doi: 10.1038/nrmicro.2016.48Debbink K., Lindesmith L.C., Donaldson E.F., Baric R.S. Norovirus immunity and the great escape. PLoS Pathog., 2012, vol. 8, no. 10: e1002921. doi: 10.1371/journal.ppat.1002921Deng Y., He T., Li B., Yuan H., Zhang F., Wu H., Ning J., Zhang Y., Zhai A., Wu C. Linear epitopes on the capsid protein of norovirus commonly elicit high antibody response among past-infected individuals. Virol. J., 2023, vol. 20, no. 1: 115. doi: 10.1186/s12985-023-02087-yDesai R., Hembree C.D., Handel A., Matthews J.E., Dickey B.W., McDonald S., Hall A.J., Parashar U.D., Leon J.S., Lopman B. Severe outcomes are associated with genogroup 2 genotype 4 norovirus outbreaks: a systematic literature review. Clin. Infect. Dis., 2012, vol. 55, no. 2, pp. 189–193. doi: 10.1093/cid/cis372Dinu S., Oprea M., Iordache R.I., Rusu L.C., Usein C.R. Genome characterisation of norovirus GII.P17-GII.17 detected during a large gastroenteritis outbreak in Romania in 2021. Arch. Virol., 2023, vol. 168, no. 4: 116. doi: 10.1007/s00705-023-05741-6Division of Viral Diseases NCfI, Respiratory Diseases CfDC, Prevention. Updated norovirus outbreak management and disease prevention guidelines. MMWR Recomm. Rep., 2011, vol. 60, pp. 1–18.Donaldson E.F., Lindesmith L.C., Lobue A.D., Baric R.S. Norovirus pathogenesis: mechanisms of persistence and immune evasion in human populations. Immunol. Rev., 2008, vol. 225, pp. 190–211. doi: 10.1111/j.1600-065X.2008.00680.xEpifanova N.V., Sashina T.A., Morozova O.V., Oparina S.V., Novikova N.A. An increase in prevalence of recombinant GII.3[P12] norovirus in sporadic acute diarrhea in children in Nizhny Novgorod, Russia, 2018–2021. Virus Genes, 2022, vol. 58, no. 5, pp. 467–472. doi: 10.1007/s11262-022-01919-3Ettayebi K., Hardy M.E. Norwalk virus nonstructural protein p48 forms a complex with the SNARE regulator VAP-A and prevents cell surface expression of vesicular stomatitis virus G protein. J. Virol., 2003, vol. 77, no. 21, pp. 11790–11797. doi: 10.1128/jvi.77.21.11790-11797.2003Fernandez-Vega V., Sosnovtsev S.V., Belliot G., King A.D., Mitra T., Gorbalenya A., Green K.Y. Norwalk virus N-terminal nonstructural protein is associated with disassembly of the Golgi complex in transfected cells. J. Virol., 2004, vol. 78, no. 9, pp. 4827–4837. doi: 10.1128/jvi.78.9.4827-4837.2004Ford-Siltz L.A., Tohma K., Kihn K., Kendra J.A., Deredge D., Wintrode P., Gao Y., Parra G.I. Characterization of cross-reactive, non-neutralizing monoclonal antibodies against a pandemic GII.4 norovirus variant. Microbiol. Spectr., 2024, vol. 12, no. 12: e0114324. doi: 10.1128/spectrum.01143-24Glass P.J., Zeng C.Q., Estes M.K. Two Nonoverlapping domains on the norwalk virus open reading frame 3 (ORF3) protein are involved in the formation of the phosphorylated 35K protein and in ORF3-capsid protein interactions. J. Virol., 2003, vol. 77, no. 6, pp. 3569–3577. doi: 10.1128/jvi.77.6.3569-3577.2003Glass P.J., White L.J., Ball J.M., Leparc-Goffart I., Hardy M.E., Estes M.K. Norwalk virus open reading frame 3 encodes a minor structural protein. J. Virol., 2000, vol. 74, no. 14, pp. 6581–6591. doi: 10.1128/jvi.74.14.6581-6591.2000Glass R.I., Parashar U.D., Estes M.K. Norovirus gastroenteritis. N. Engl. J. Med., 2009, vol. 361, no. 18, pp. 1776–1785. doi: 10.1056/NEJMra0804575Graziano V.R., Wei J., Wilen C.B. Norovirus Attachment and Entry. Viruses, 2019, vol. 11, no. 6: 495. doi: 10.3390/v11060495Green K.Y., Kaufman S.S., Nagata B.M., Chaimongkol N., Kim D.Y., Levenson E.A., Tin C.M., Yardley A.B., Johnson J.A., Barletta A.B.F., Khan K.M., Yazigi N.A., Subramanian S., Moturi S.R., Fishbein T.M., Moore I.N., Sosnovtsev S.V. Human norovirus targets enteroendocrine epithelial cells in the small intestine. Nat. Commun., 2020, vol. 11, no. 1: 2759. doi: 10.1038/s41467-020-16491-3Haga K., Fujimoto A., Takai-Todaka R., Miki M., Doan Y.H., Murakami K., Yokoyama M., Murata K., Nakanishi A., Katayama K. Functional receptor molecules CD300lf and CD300ld within the CD300 family enable murine noroviruses to infect cells. Proc. Natl Acad. Sci. USA, 2016, vol. 113, no. 41, pp. E6248–E6255. doi: 10.1073/pnas.1605575113Hanajiri R., Sani G.M., Saunders D., Hanley P.J., Chopra A., Mallal S.A., Sosnovtsev S.V., Cohen J.I., Green K.Y., Bollard C.M., Keller M.D. Generation of norovirus-specific T cells from human donors with extensive cross-reactivity to variant sequences: implications for immunotherapy. J. Infect. Dis., 2020, vol. 221, no. 4, pp. 578–588. doi: 10.1093/infdis/jiz491Hansman G.S., Natori K., Shirato-Horikoshi H., Ogawa S., Oka T., Katayama K., Tanaka T., Miyoshi T., Sakae K., Kobayashi S., Shinohara M., Uchida K., Sakurai N., Shinozaki K., Okada M., Seto Y., Kamata K., Nagata N., Tanaka K., Miyamura T., Takeda N. Genetic and antigenic diversity among noroviruses. J. Gen. Virol., 2006, vol. 87, pp. 909–919. doi: 10.1099/vir.0.81532-0Hardy M.E. Norovirus protein structure and function. FEMS Microbiol. Lett., 2005, vol. 253, no. 1, pp. 1–8. doi: 10.1016/j.femsle.2005.08.031He T., Deng Y., Zhang F., Zhang J., Zhu L., Wang Q., Ning J., Wu H., Yuan H., Li B., Wu C. Characteristics of Norovirus capsid protein-specific CD8+ T-Cell responses in previously infected individuals. Virulence, 2024, vol. 15, no. 1: 2360133. doi: 10.1080/21505594.2024.2360133Hemming M., Rasanen S., Huhti L., Paloniemi M., Salminen M., Vesikari T. Major reduction of rotavirus, but not norovirus, gastroenteritis in children seen in hospital after the introduction of RotaTeq vaccine into the National Immunization Programme in Finland. Eur. J. Pediatr., 2013, vol. 172, no. 6, pp. 739–746. doi: 10.1007/s00431-013-1945-3Hoa Tran T.N., Trainor E., Nakagomi T., Cunliffe N.A., Nakagomi O. Molecular epidemiology of noroviruses associated with acute sporadic gastroenteritis in children: global distribution of genogroups, genotypes and GII.4 variants. J. Clin. Virol., 2013, vol. 56, no. 3, pp. 185–193. doi: 10.1016/j.jcv.2012.11.011Hosmillo M., Chaudhry Y., Nayak K., Sorgeloos F., Koo B.K., Merenda A., Lillestol R., Drumright L., Zilbauer M., Goodfellow I. Norovirus Replication in Human Intestinal Epithelial Cells Is Restricted by the Interferon-Induced JAK/STAT Signaling Pathway and RNA Polymerase II-Mediated Transcriptional Responses. mBio, 2020, vol. 11, no. 2: e00215-20. doi: 10.1128/mBio.00215-20Huang Z., Chen Q., Hjelm B., Arntzen C., Mason H. A DNA replicon system for rapid high-level production of virus-like particles in plants. Biotechnol. Bioeng., 2009, vol. 103, no. 4, pp. 706–714. doi: 10.1002/bit.22299Ingle H., Peterson S.T., Baldridge M.T. Distinct Effects of Type I and III Interferons on Enteric Viruses. Viruses, 2018, vol. 10, no. 1: 46. doi: 10.3390/v10010046Ishiyama R., Yoshida K., Oikawa K., Takai-Todaka R., Kato A., Kanamori K., Nakanishi A., Haga K., Katayama K. Production of infectious reporter murine norovirus by VP2 trans-complementation. J. Virol., 2024, vol. 98: e01261-23. doi: 10.1128/jvi.01261-23Jiang X., Wang M., Graham D.Y., Estes M.K. Expression, self-assembly, and antigenicity of the Norwalk virus capsid protein. J. Virol., 1992, vol. 66, no. 11, pp. 6527–6532. doi: 10.1128/JVI.66.11.6527-6532.1992Jin M., Zhou Y.K., Xie H.P., Fu J.G., He Y.Q., Zhang S., Jing H.B., Kong X.Y., Sun X.M., Li H.Y., Zhang Q., Li K., Zhang Y.J., Zhou D.Q., Xing W.J., Liao Q.H., Liu N., Yu H.J., Jiang X., Tan M., Duan Z.J. Characterization of the new GII.17 norovirus variant that emerged recently as the predominant strain in China. J. Gen. Virol., 2016, vol. 97, no. 10, pp. 2620–2632. doi: 10.1099/jgv.0.000582Johnson P.C., Mathewson J.J., DuPont H.L., Greenberg H.B. Multiple-challenge study of host susceptibility to Norwalk gastroenteritis in US adults. J. Infect. Dis., 1990, vol. 161, no. 1, pp. 18–21. doi: 10.1093/infdis/161.1.18Karandikar U.C., Crawford S.E., Ajami N.J., Murakami K., Kou B., Ettayebi K., Papanicolaou G.A., Jongwutiwes U., Perales M.A., Shia J., Mercer D., Finegold M.J., Vinjé J., Atmar R.L., Estes M.K. Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients. J. Gen. Virol., 2016, vol. 97, no. 9, pp. 2291–2300. doi: 10.1099/jgv.0.000545Kendra J.A., Tohma K., Ford-Siltz L.A., Lepore C.J., Parra G.I. Antigenic cartography reveals complexities of genetic determinants that lead to antigenic differences among pandemic GII.4 noroviruses. Proc. Natl Acad. Sci. USA, 2021, vol. 118, no. 11: e2015874118. doi: 10.1073/pnas.2015874118Kendra J.A., Tohma K., Parra G.I. Global and regional circulation trends of norovirus genotypes and recombinants, 1995–2019: A comprehensive review of sequences from public databases. Rev. Med. Virol., 2022, vol. 32, no. 5: e2354. doi: 10.1002/rmv.2354Kilic T., Koromyslova A., Hansman G.S. Structural Basis for Human Norovirus Capsid Binding to Bile Acids. J. Virol., 2019, vol. 93, no. 2: e01581-18. doi: 10.1128/JVI.01581-18Koo H.L., Neill F.H., Estes M.K., Munoz F.M., Cameron A., DuPont H.L., Atmar R.L. Noroviruses: the most common pediatric viral enteric pathogen at a large university hospital after introduction of rotavirus vaccination. J. Pediatric. Infect. Dis. Soc., 2013, vol. 2, no. 1, pp. 57–60. doi: 10.1093/jpids/pis070Larsson M.M., Rydell G.E., Grahn A., Rodriguez-Diaz J., Akerlind B., Hutson A.M., Estes M.K., Larson G., Svensson L. Antibody prevalence and titer to norovirus (genogroup II) correlate with secretor (FUT2) but not with ABO phenotype or Lewis (FUT3) genotype. J. Infect. Dis., 2006, vol. 194, no. 10, pp. 1422–1427. doi: 10.1086/508430Li Y., Yu P., Qu C., Li P., Li Y., Ma Z., Wang W., de Man R.A., Peppelenbosch M.P., Pan Q. MDA5 against enteric viruses through induction of interferon-like response partially via the JAK-STAT cascade. Antiviral Res., 2020, vol. 176: 104743. doi: 10.1016/j.antiviral.2020.104743Lin S.C., Qu L., Ettayebi K., Crawford S.E., Blutt S.E., Robertson M.J., Zeng X.L., Tenge V.R., Ayyar B.V., Karandikar U.C., Yu X., Coarfa C., Atmar R.L., Ramani S., Estes M.K. Human norovirus exhibits strain-specific sensitivity to host interferon pathways in human intestinal enteroids. Proc. Natl Acad. Sci. USA, 2020, vol. 117, no. 38, pp. 23782–23793. doi: 10.1073/pnas.2010834117Lindesmith L., Moe C., Marionneau S., Ruvoen N., Jiang X., Lindblad L., Stewart P., LePendu J., Baric R. Human susceptibility and resistance to Norwalk virus infection. Nat. Med., 2003, vol. 9, no. 5, pp. 548–553. doi: 10.1038/nm860Lindesmith L.C., Brewer-Jensen P.D., Mallory M.L., Jensen K., Yount B.L., Costantini V., Collins M.H., Edwards C.E., Sheahan T.P., Vinjé J., Baric R.S. Virus-Host Interactions Between Nonsecretors and Human Norovirus. Cell. Mol. Gastroenterol. Hepatol., 2020, vol. 10, no. 2, pp. 245–267. doi: 10.1016/j.jcmgh.2020.03.006Lindesmith L.C., Costantini V., Swanstrom J., Debbink K., Donaldson E.F., Vinjé J., Baric R.S. Emergence of a norovirus GII.4 strain correlates with changes in evolving blockade epitopes. J. Virol., 2013, vol. 87, no. 5, pp. 2803–2813. doi: 10.1128/JVI.03106-12Lindesmith L.C., Donaldson E.F., Lobue A.D., Cannon J.L., Zheng D.-P., Vinje J., Baric R.S. Mechanisms of GII.4 norovirus persistence in human populations. PLoS Med., 2008, vol. 5, no. 2: e31. doi: 10.1371/journal.pmed.0050031Liu J., Wang Z., Ma J., Ji S., Huo Y. Identification of a norovirus GII-specific antigenic epitope. Arch. Virol., 2024, vol. 169, no. 6: 131. doi: 10.1007/s00705-024-06060-0Liu Z., Zhang M., Shen Z., Chen H., Zhang W., Xu X., Lai Z., Sun W., Zhao Z., Zhang J. The coordinating role of the human norovirus minor capsid protein VP2 is essential to functional change and nuclear localization of the major capsid protein VP1. Arch. Virol., 2019, vol. 164, pp. 1173–1180. doi: 10.1007/s00705-019-04192-2Luttermann C., Meyers G. A bipartite sequence motif induces translation reinitiation in feline calicivirus RNA. J. Biol. Chem., 2007, vol. 282, no. 10, pp. 7056–7065. doi: 10.1074/jbc.M608948200Mallory M.L., Lindesmith L.C., Graham R.L., Baric R.S. GII.4 Human Norovirus: Surveying the Antigenic Landscape. Viruses, 2019, vol. 11, no. 2: 177. doi: 10.3390/v11020177Malm M., Uusi-Kerttula H., Vesikari T., Blazevic V. High serum levels of norovirus genotype-specific blocking antibodies correlate with protection from infection in children. J. Infect. Dis., 2014, vol. 210, no. 11, pp. 1755–1762. doi: 10.1093/infdis/jiu361Mboko W.P., Chhabra P., Valcarce M.D., Costantini V., Vinjé J. Advances in understanding of the innate immune response to human norovirus infection using organoid models. J. Gen. Virol., 2022, vol. 103, no. 1: 001720. doi: 10.1099/jgv.0.001720Mesev E.V., LeDesma R.A., Ploss A. Decoding type I and III interferon signalling during viral infection. Nat. Microbiol., 2019, vol. 4, no. 6, pp. 914–924. doi: 10.1038/s41564-019-0421-xNewman K.L., Leon J.S. Norovirus immunology: Of mice and mechanisms. Eur. J. Immunol., 2015, vol. 45, no. 10, pp. 2742–2757. doi: 10.1002/eji.201545512Newman K.L., Moe C.L., Kirby A.E., Flanders W.D., Parkos C.A., Leon J.S. Human norovirus infection and the acute serum cytokine response. Clin. Exp. Immunol., 2015, vol. 182, no. 2, pp. 195–203. doi: 10.1111/cei.12681Noel J.S., Fankhauser R.L., Ando T., Monroe S.S., Glass R.I. Identification of a distinct common strain of «Norwalk-like viruses» having a global distribution. J. Infect. Dis., 1999, vol. 179, no. 6, pp. 1334–1344. doi: 10.1086/314783Nordgren J., Svensson L. Genetic Susceptibility to Human Norovirus Infection: An Update. Viruses, 2019, vol. 11, no. 3: 226. doi: 10.3390/v11030226Nurminen K., Blazevic V., Huhti L., Räsänen S., Koho T., Hytönen V.P., Vesikari T. Prevalence of norovirus GII-4 antibodies in Finnish children. J. Med. Virol., 2011, vol. 83, no. 3, pp. 525–531. doi: 10.1002/jmv.21990Omatola C.A., Mshelbwala P.P., Okolo M.-L.O., Onoja A.B., Abraham J.O., Adaji D.M., Samson S.O., Okeme T.O., Aminu R.F., Akor M.E., Ayeni G., Muhammed D., Akoh P.Q., Ibrahim D.S., Edegbo E., Yusuf L., Ocean H.O., Akpala S.N., Musa O.A., Adamu A.M. Noroviruses: Evolutionary Dynamics, Epidemiology, Pathogenesis, and Vaccine Advances — A Comprehensive Review. Vaccines, 2024, vol. 12: 590. doi: 10.3390/vaccines12060590Oparina S.V., Epifanova N.V., Novikova N.A. Phylogenetic analysis of noroviruses basedon rna-dependent rna polymerase GII.P16 gene sequences. Opera Medica et Physiologica, 2022, vol. 9, no. 3, pp. 87–97. doi: 10.24412/2500-2295-2022-3-87-97Orchard R.C., Wilen C.B., Doench J.G., Baldridge M.T., McCune B.T., Lee Y.C., Lee S., Pruett-Miller S.M., Nelson C.A., Fremont D.H., Virgin H.W. Discovery of a proteinaceous cellular receptor for a norovirus. Science, 2016, vol. 353, no. 6302, pp. 933–936. doi: 10.1126/science.aaf1220Parra G.I., Squires R.B., Karangwa C.K., Johnson J.A., Lepore C.J., Sosnovtsev S.V., Green K.Y. Static and Evolving Norovirus Genotypes: Implications for Epidemiology and Immunity. PLoS Pathog., 2017, vol. 13, no. 1: e1006136. doi: 10.1371/journal.ppat.1006136Parrino T.A., Schreiber D.S., Trier J.S., Kapikian A.Z., Blacklow N.R. Clinical immunity in acute gastroenteritis caused by Norwalk agent. N. Engl. J. Med., 1977, vol. 297, no. 2, pp. 86–89. doi: 10.1056/NEJM197707142970204Pattekar A., Mayer L.S., Lau C.W., Liu C., Palko O., Bewtra M., Consortium H., Lindesmith L.C., Brewer-Jensen P.D., Baric R.S., Betts M.R., Naji A., Wherry E.J., Tomov V.T. Norovirus-Specific CD8+ T Cell Responses in Human Blood and Tissues. Cell. Mol. Gastroenterol. Hepatol., 2021, vol. 11, no. 5, pp. 1267–1289. doi: 10.1016/j.jcmgh.2020.12.012Payne D.C., Vinjé J., Szilagyi P.G., Edwards K.M., Staat M.A., Weinberg G.A., Hall C.B., Chappell J., Bernstein D.I., Curns A.T., Wikswo M., Shirley S.H., Hall A.J., Lopman B., Parashar U.D. Norovirus and medically attended gastroenteritis in U.S. children. N. Engl. J. Med., 2013, vol. 368, no. 12, pp. 1121–1130. doi: 10.1056/NEJMsa1206589Ponterio E., Mariotti S., Tabolacci C., Ruggeri F.M., Nisini R. Virus like particles of GII.4 norovirus bind Toll Like Receptors 2 and 5. Immunol. Lett., 2019, vol. 215, pp. 40–44. doi: 10.1016/j.imlet.2019.05.016Ponterio E., Petrizzo A., Di Bartolo I., Buonaguro F.M., Buonaguro L., Ruggeri F.M. Pattern of activation of human antigen presenting cells by genotype GII.4 norovirus virus-like particles. J. Transl. Med., 2013, vol. 11: 127. doi: 10.1186/1479-5876-11-127Prasad B.V., Rothnagel R., Jiang X., Estes M.K. Three-dimensional structure of baculovirus-expressed Norwalk virus capsids. J. Virol., 1994, vol. 68, no. 8, pp. 5117–5125. doi: 10.1128/JVI.68.8.5117-5125.1994Ramani S., Neill F.H., Opekun A.R., Gilger M.A., Graham D.Y., Estes M.K., Atmar R.L. Mucosal and Cellular Immune Responses to Norwalk Virus. J. Infect. Dis., 2015, vol. 212, no. 3, pp. 397–405. doi: 10.1093/infdis/jiv053Ramani S., Atmar R.L., Estes M.K. Epidemiology of human noroviruses and updates on vaccine development. Curr. Opin. Gastroenterol., 2014, vol. 30, no. 1, pp. 25–33. doi: 10.1097/MOG.0000000000000022Reeck A., Kavanagh O., Estes M.K., Opekun A.R., Gilger M.A., Graham D.Y., Atmar R.L. Serological correlate of protection against norovirus-induced gastroenteritis. J. Infect. Dis., 2010, vol. 202, no. 8, pp. 1212–1218. doi: 10.1086/656364Roth A.N., Karst S.M. Norovirus mechanisms of immune antagonism. Curr. Opin. Virol., 2016, vol. 16, pp. 24–30. doi: 10.1016/j.coviro.2015.11.005Ryder R.W., Singh N., Reeves W.C., Kapikian A.Z., Greenberg H.B., Sack R.B. Evidence of immunity induced by naturally acquired rotavirus and Norwalk virus infection on two remote Panamanian islands. J. Infect. Dis., 1985, vol. 151, no. 1, pp. 99–105. doi: 10.1093/infdis/151.1.99Santi L., Batchelor L., Huang Z., Hjelm B., Kilbourne J., Arntzen C.J., Chen Q., Mason H.S. An efficient plant viral expression system generating orally immunogenic Norwalk virus-like particles. Vaccine, 2008, vol. 26, no. 15, pp. 1846–1854. doi: 10.1016/j.vaccine.2008.01.053Seah E.L., Gunesekere I.C., Marshall J.A., Wright P.J. Variation in ORF3 of genogroup 2 Norwalk-like viruses. Arch. Virol., 1999, vol. 144, no. 5, pp. 1007–1014. doi: 10.1007/s007050050563Sharp T.M., Crawford S.E., Ajami N.J., Neill F.H., Atmar R.L., Katayama K., Utama B., Estes M.K. Secretory pathway antagonism by calicivirus homologues of Norwalk virus nonstructural protein p22 is restricted to noroviruses. Virol. J., 2012, vol. 9: 181. doi: 10.1186/1743-422X-9-181Sharp T.M., Guix S., Katayama K., Crawford S.E., Estes M.K. Inhibition of cellular protein secretion by norwalk virus nonstructural protein p22 requires a mimic of an endoplasmic reticulum export signal. PLoS One, 2010, vol. 5, no. 10: e13130. doi: 10.1371/journal.pone.0013130Siebenga J.J., Lemey P., Kosakovsky Pond S.L., Rambaut A., Vennema H., Koopmans M. Phylodynamic reconstruction reveals norovirus GII.4 epidemic expansions and their molecular determinants. PLoS Pathog., 2010, vol. 6, no. 5: e1000884. doi: 10.1371/journal.ppat.1000884Simmons K., Gambhir M., Leon J., Lopman B. Duration of immunity to norovirus gastroenteritis. Emerg. Infect. Dis., 2013, vol. 19, no. 8, pp. 1260–1267. doi: 10.3201/eid1908.130472Sosnovtsev S.V., Green K.Y. Identification and genomic mapping of the ORF3 and VPg proteins in feline calicivirus virions. Virology, 2000, vol. 277, no. 1, pp. 193–203. doi: 10.1006/viro.2000.0579Souza M., Cheetham S.M., Azevedo M.S., Costantini V., Saif L.J. Cytokine and antibody responses in gnotobiotic pigs after infection with human norovirus genogroup II.4 (HS66 strain). J. Virol., 2007, vol. 81, no. 17, pp. 9183–9192. doi: 10.1128/JVI.00558-07Su L., Huang W., Neill F.H., Estes M.K., Atmar R.L., Palzkill T. Mapping human norovirus antigens during infection reveals the breadth of the humoral immune response. N.P.J. Vaccines, 2023, vol. 8, no. 1: 87. doi: 10.1038/s41541-023-00683-1Tan M., Huang P., Meller J., Zhong W., Farkas T., Jiang X. Mutations within the P2 domain of norovirus capsid affect binding to human histo-blood group antigens: evidence for a binding pocket. J. Virol., 2003, vol. 77, no. 23, pp. 12562–12571. doi: 10.1128/jvi.77.23.12562-12571.2003Tan M., Jiang X. The p domain of norovirus capsid protein forms a subviral particle that binds to histo-blood group antigen receptors. J. Virol., 2005, vol. 79, no. 22, pp. 14017–14030. doi: 10.1128/JVI.79.22.14017-14030.2005Tohma K., Ford-Siltz L.A., Kendra J.A., Parra G.I. Dynamic immunodominance hierarchy of neutralizing antibody responses to evolving GII.4 noroviruses. Cell Rep., 2022, vol. 39, no. 2: 110689. doi: 10.1016/j.celrep.2022.110689Tohma K., Lepore C.J., Gao Y., Ford-Siltz L.A., Parra G.I. Population Genomics of GII.4 Noroviruses Reveal Complex Diversification and New Antigenic Sites Involved in the Emergence of Pandemic Strains. mBio, 2019, vol. 10, no. 5: e02202-19. doi: 10.1128/mBio.02202-19Treanor J.J., Jiang X., Madore H.P., Estes M.K. Subclass-specific serum antibody responses to recombinant Norwalk virus capsid antigen (rNV) in adults infected with Norwalk, Snow Mountain, or Hawaii virus. J. Clin. Microbiol., 1993, vol. 31, no. 6, pp. 1630–1634. doi: 10.1128/jcm.31.6.1630-1634.1993Tsukamoto B., Kurebayashi Y., Takahashi T., Abe Y., Ota R., Wakabayashi Y., Nishiie A., Minami A., Suzuki T., Takeuchi H. VP1 of human and murine noroviruses recognizes glycolipid sulfatide via the P domain. J. Biochem., 2024, vol. 176, no. 4, pp. 299–312. doi: 10.1093/jb/mvae051Villabruna N., Izquierdo-Lara R.W., Schapendonk C.M.E., de Bruin E., Chandler F., Thao T.T.N., Westerhuis B.M., van Beek J., Sigfrid L., Giaquinto C., Goossens H., Bielicki J.A., Vasconcelos M.K., Fraaij P.L.A., Koopmans M.P.G., de Graaf M. Profiling of humoral immune responses to norovirus in children across Europe. Sci. Rep., 2022, vol. 12, no. 1: 14275. doi: 10.1038/s41598-022-18383-6Vongpunsawad S., Venkataram Prasad B.V., Estes M.K. Norwalk virus minor capsid protein VP2 associates within the VP1 Shell domain. J. Virol., 2013, vol. 87, no. 9, pp. 4818–4825. doi: 10.1128/JVI.03508-12Winder N., Gohar S., Muthana M. Norovirus: An Overview of Virology and Preventative Measures. Viruses, 2022, vol. 14, no. 12: 2811. doi: 10.3390/v14122811Wyatt R.G., Dolin R., Blacklow N.R., DuPont H.L., Buscho R.F., Thornhill T.S., Kapikian A.Z., Chanock R.M. Comparison of three agents of acute infectious nonbacterial gastroenteritis by cross-challenge in volunteers. J. Infect. Dis., 1974, vol. 129, no. 6, pp. 709–714. doi: 10.1093/infdis/129.6.709Xue L., Wu Q., Kou X., Cai W., Zhang J., Guo W. Genome characterization of a GII.6 norovirus strain identified in China. Infect. Genet. Evol., 2015, vol. 31, pp. 110–117. doi: 10.1016/j.meegid.2015.01.027Zhang P., Hao C., Di X., Chuizhao X., Jinsong L., Guisen Z., Hui L., Zhaojun D. Global prevalence of norovirus gastroenteritis after emergence of the GII.4 Sydney 2012 variant: a systematic review and meta-analysis. Front. Public Health, 2024, vol. 12: 1373322. doi: 10.3389/fpubh.2024.1373322Zharova A.-M.D., Talayev V.Yu., Perenkov A.D., Zaichenko I.Ye., Svetlova M.V., Babaykina O.N., Voronina E.V., Lapin V.A., Novikov V.V. In silico analysis of the antigenic properties of norovirus GII.4 Sydney[P16] VP1 protein. Opera Medica et Physiologica, 2023, vol. 10, no. 3, pp. 140–151. doi: 10.24412/2500-2295-2023-3-140-151Zheng Z., Li Y., Zhang M., Liu Y., Fu M., Gong S., Hu Q. Human Norovirus NTPase Antagonizes Interferon-β Production by Interacting With IkB Kinase ε. Front. Microbiol., 2021, vol. 12: 687933. doi: 10.3389/fmicb.2021.687933Zhu S., Regev D., Watanabe M. Identification of immune and viral correlates of norovirus protective immunity through comparative study of intra-cluster norovirus strains. PLoS Pathog., 2013, vol. 9, no. 9: e1003592. doi: 10.1371/journal.ppat.1003592