Vestnik of the Far East Branch of the Russian Academy of SciencesVestnik of the Far East Branch of the Russian Academy of SciencesВестник Дальневосточного отделения Российской академии наук0869-7698The Russian Academy of Sciences67604810.31857/S0869769824020074ldifvhBiological SciencesБиологические наукиResearch ArticleSignificance of antibody detection to individual B-epitopes of envelope proteins of hepatitis C virusЗначимость обнаружения антител к отдельным В-эпитопам оболочечных белков вируса гепатита Сhttps://orcid.org/0000-0001-8544-7482StuchinskayaMaya D.СтучинскаяМайя Денисовна
Russian Federation

Graduate Student; Junior Researcher

аспирант; младший научный сотрудник

mayastaya@mail.ruhttps://orcid.org/0000-0002-1323-5568NikolaevaLyudmila I.НиколаеваЛюдмила Ивановна
Russian Federation

Doctor of Sciences in Biology, Leading Researcher

доктор биологических наук, ведущий научный сотрудник

l.i.nikolaeva@mail.ruhttps://orcid.org/0000-0002-2486-4554ShevchenkoNadezhda G.ШевченкоНадежда Григорьевна
Russian Federation

Junior Researcher

младший научный сотрудник

dr.nadya@inbox.ruhttps://orcid.org/0000-0002-2154-2904SapronovGeorgy V.СапроновГеоргий Витальевич
Russian Federation

Candidate of Sciences in Medicine, Senior Researcher; Associate Professor

кандидат медицинских наук, старший научный сотрудник; доцент

g-sapronov@mail.ruhttps://orcid.org/0000-0001-8382-7262ShastinaNatalya S.ШастинаНаталья Сергеевна
Russian Federation

Candidate of Sciences in Chemistry, Associate Professor

кандидат химических наук, доцент

inosit@yandex.ruMIREA - Russian Technology UniversityМИРЭА - Российский технологический университетN. F. Gamaleya National Research Center for Epidemiology and MicrobiologyНИЦЭМ им. Н. Ф. ГамалеиRussian Medical Academy of Continuing Professional EducationРМАНПО150420242707928022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-7698/article/view/676048

Hepatitis C virus (HCV) is hepatotropic viruses, causing chronic infection, which can lead to liver failure, cirrhosis, and hepatocellular carcinoma. The two viral envelope glycoproteins E1 and E2 mediate the virus entry into host cells, and they are the targets of virus-neutralizing antibodies, which play an important role in limiting infection. The aim of the study was to analyze infected human antibody response to peptides reproducing B-cell epitopes of HCV envelope proteins to assess their possible association with virus elimination. The synthesis of three peptides from envelope proteins was carried out by the solid phase method. The immunoreactivity of the peptides was studied with blood sera from 63 participants with viral hepatitis C. The amino acid sequences of the peptides corresponded to region 244–259 and 313–324 of the E1 protein and 395–411 of the E2 protein. Peptide immunoreactivity was assessed by enzyme-linked immunosorbent assay (ELISA) using blood sera of 63 participants with acute and chronic hepatitis C. According to the results of ELISA, it was found that antibodies were detected in 55,6% (sampling error 6,3%) of participants. If the presence of an antibody titer was 1:80 or higher to the analyzed peptides, then the most participants completed therapy with a sustained virological response or acute hepatitis with the virus elimination. That may indicate the potential significance of the presence of antibodies to B-cell epitopes of HCV envelope proteins in this titer of high for a positive outcome of acute hepatitis C and therapy with direct antiviral drugs.

Вирус гепатита С (ВГС) – гепатотропный вирус, хроническая инфекция которого может привести к печеночной недостаточности, циррозу печени и гепатоцеллюлярной карциноме. Два вирусных оболочечных гликопротеина E1 и E2 опосредуют проникновение вируса в клетки хозяина и являются мишенями для вируснейтрализующих антител, играющих важную роль в ограничении инфекции. Цель исследования – проанализировать наличие антител к пептидам, воспроизводящим В-клеточные эпитопы оболочечных белков ВГС, для оценки их возможной ассоциации с элиминацией вируса. Синтез трех пептидов из оболочечных белков вируса проводился твердофазным методом. Аминокислотные последовательности пептидов соответствовали участкам 244–259 и 313–324 белка Е1 и 395–411 белка Е2. Иммунореактивность пептидов была проанализирована методом твердофазного иммуноферментного анализа (ИФА) с использованием сывороток крови 63 участников с острым и хроническим гепатитом С. По результатам ИФА установлено, что антитела выявляются у 55,6% участников (ошибка выборки 6,3%). Если титр антител к анализируемым пептидам был 1:80 или превышал его, то большинство участников завершали терапию с достижением устойчивого вирусологического ответа или наблюдался острый гепатит с элиминацией вируса. Этот факт может свидетельствовать о потенциальной значимости наличия антител к анализируемым В-клеточным эпитопам оболочечных белков ВГС в титре 1:80 или выше для позитивного исхода острой фазы инфекции и терапии препаратами прямого противовирусного действия.

synthetic peptidesВ-cell epitopesenvelope proteins of hepatitis C virusimmunoreactivityсинтетические пептидыВ-клеточные эпитопыоболочечные белки вируса гепатита СиммунореактивностьWorld Health Organization. Global Hepatitis Report, 2017 / World Health Organization. Geneva, Switzerland; 2017. 83 p. URL: https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/ (accessed on 20.03.2023).World Health Organization. Global Hepatitis Report, 2017 / World Health Organization. Geneva, Switzerland, 2017. 83 p. URL: https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/ (accessed on 20.03.2023).Wang R., Suzuki S., et al. Induction of broadly neutralizing antibodies using a secreted form of the hepatitis C virus E1, E2 heterodimer as a vaccine candidate. Proceedings of the National Academy of Sciences. 2022;119(11).Wang R., Suzuki S. et al. Induction of broadly neutralizing antibodies using a secreted form of the hepatitis C virus E1, E2 heterodimer as a vaccine candidate // PNAS. 2022. Vol. 119, N11.Colpitts C. C., Tsai P. L., Zeisel M. B. Hepatitis C virus entry: An intriguingly complex and highly regulated process. International Journal of Molecular Sciences. 2020; 21(6):2091.Colpitts C. C., Tsai P. L., Zeisel M. B. Hepatitis C virus entry: An intriguingly complex and highly regulated process // Int. J. Mol. Sci. 2020. Vol. 21. P. 2091.Sepulveda-Crespo D., Resino S., Martinez I. Hepatitis C virus vaccine design: focus on the humoral immune response. Journal of Biomedical Science. 2020;27:78.Sepulveda-Crespo D., Resino S., Martinez I. Hepatitis C virus vaccine design: focus on the humoral immune response // J. Biomed. Sci. 2020. Vol. 27. P. 78.Raghuraman S., Park H., Osburn W. O., Winkelstein E., Edlin B. R., Rehermann B. Spontaneous clearance of chronic hepatitis C virus infection is associated with appearance of neutralizing antibodies and reversal of T-cell exhaustion. The Journal of Infectious Diseases. 2012;205(5):763–771.Raghuraman S., Park H., Osburn W. O., Winkelstein E., Edlin B. R., Rehermann B. Spontaneous clearance of chronic hepatitis C virus infection is associated with appearance of neutralizing antibodies and reversal of T-cell exhaustion // J. Infect. Dis. 2012. Vol. 205, N5. P. 763–771.Pestka J. M., Zeisel M. B., Bläser E. et al. Rapid induction of virus-neutralizing antibodies and viral clearance in a single-source outbreak of hepatitis C. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(14):6025–6030.Pestka J. M., Zeisel M. B., Bläser E. et al. Rapid induction of virus-neutralizing antibodies and viral clearance in a single-source outbreak of hepatitis C // Proc. Natl. Acad. Sci. U. S. A. 2007. Vol. 104, N14. P. 6025–6030.Quadeer A. A., Louie R. H.Y., McKay M. R. Identifying immunologically-vulnerable regions of the HCV E2 glycoprotein and broadly neutralizing antibodies that target them. Nature Communications. 2019;10(1):2073.Quadeer A. A., Louie R. H.Y., McKay M. R. Identifying immunologically-vulnerable regions of the HCV E2 glycoprotein and broadly neutralizing antibodies that target them // Nat. Com. 2019. Vol. 10. P. 2073.Cocquerel L., Meunier J. C., Op de Beeck A., Bonte D., Wychowski C., Dubuisson J. Coexpression of hepatitis C virus envelope proteins E1 and E2 in cis improves the stability of membrane insertion of E2. The Journal of General Virology. 2001;82(7):1629–1635.Cocquerel L., Meunier J. C., Op de Beeck A., Bonte D., Wychowski C., Dubuisson J. Coexpression of hepatitis C virus envelope proteins E1 and E2 in cis improves the stability of membrane insertion of E2 // J. Gen. Virol. 2001. Vol. 82, № 7. P. 1629–1635.Keck Z. Y., Sung V. M., Perkins S. et al. Human monoclonal antibody to hepatitis C virus E1 glycoprotein that blocks virus attachment and viral infectivity. Journal of Virology. 2004;78(13):7257–7263.Keck Z. Y., Sung V. M.H., Perkins S. et al. Human monoclonal antibody to hepatitis C virus E1 glycoprotein that blocks virus attachment and viral infectivity // J. Virol. 2004. Vol. 78, N13. P. 7257–7263.Mesalam A. A., Desombere I., Farhoudi A. et al. Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1. Virology. 2018;514:30–41.Mesalam A. A., Desombere I., Farhoudi A. et al. Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1 // Virology. 2018. Vol. 514. P. 30–41.Tzarum N., Wilson I. A., Law M. The neutralizing face of hepatitis C virus E2 envelope glycoprotein. Frontiers in Immunology. 2018;9:1315.Tzarum N., Wilson I. A., Law M. The neutralizing face of hepatitis C virus E2 envelope glycoprotein // Front. Immunol. 2018. Vol. 9. P. 1315.Farci P., Shimoda A., Wong D. et al. Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein. Proceedings of the National Academy of Sciences of the United States of America. 1996;93(26):15394–15399.Farci P., Shimoda A., Wong D. et al. Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein // Proc. Natl. Acad. Sci. U. S. A. 1996. Vol. 93, N26. P. 15394–15399.Nikolaeva L. I., Petrova E. V., Finogenova M. P. Antibodies to envelope proteins E1 and E2 in people infected with hepatitis C virus. Epidemiology and Vaccinal Prevention. 2006;1(26):37–41. (In Russ.).Николаева Л. И., Петрова Е. В., Финогенова М. П. Антитела к оболочечным белкам Е1 и Е2 у людей, инфицированных вирусом гепатита С // Эпидемиология и вакцинопрофилактика. 2006. Т. 1, № 26. С. 37–41.Sobolev B. N., Poroikov V. V., Olenina L. V., Kolesanova E. F., Archakov A. I. Comparative analysis of amino acid sequences from envelope proteins isolated from different hepatitis C virus variants: possible role of conservative and variable regions. Journal of Viral Hepatitis. 2000;7(5):368–374.Sobolev B. N., Poroikov V. V., Olenina L. V., Kolesanova E. F., Archakov A. I. Comparative analysis of amino acid sequences from envelope proteins isolated from different hepatitis C virus variants: possible role of conservative and variable regions // J. Viral. Hepat. 2000. Vol. 7, N5. P. 368–374.Zibert A., Kraas W., Ross R. S. et al. Immunodominant B-cell domains of hepatitis C virus envelope proteins E1 and E2 identified during early and late time points of infection. Journal of Hepatology. 1999;30(2):177–184.ZibertA., Kraas W., Ross R. S., Meisel H., Lechner S., Jung G., Roggendorf M. Immunodominant B-cell domains of hepatitis C virus envelope proteins E1 and E2 identified during early and late time points of infection // J. Hepatol. 1999. Vol. 30, N2. P. 177–184.Garcia J. E., Puentes A., Súarez J. et al. Hepatitis C virus (HCV) E1 and E2 protein regions that specifically bind to HepG2 cells. Journal of Hepatology. 2002;36(2):254–262.Garcia J. E., Puentes A., Súarez J., López R., Vera R., Rodríguez L. E., Ocampo M., Curtidor H., Guzman F., Urquiza M., Patarroyo M. E. Hepatitis C virus (HCV) E1 and E2 protein regions that specifically bind to HepG2 cells // J. Hepatol. 2002. Vol. 36, N2. P. 254–262.Garry R. F., Dash S. Proteomics computational analyses suggest that hepatitis C virus E1 and pestivirus E2 envelope glycoproteins are truncated class II fusion proteins. Virology. 2003;307(2):255–265.Garry R. F., Dash S. Proteomics computational analyses suggest that hepatitis C virus E1 and pestivirus E2 envelope glycoproteins are truncated class II fusion proteins // Virology. 2003 Vol. 307, N2. P. 255–265.Giang E., Dorner M., Prentoe J. C. et al. Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(16):6205–6210.Giang E., Dorner M., Prentoe J. C., Dreux M., Evans M. J., Bukh J., Rice C. M., Ploss A., Burton D. R., Law M. Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus // Proc. Natl. Acad. Sci. U. S. A. 2012. Vol. 109, N16. P. 6205–6210.Owsianka A., Clayton R. F., Loomis-Price L.D., McKeating J.A., Patel A. H. Functional analysis of hepatitis C virus E2 glycoproteins and virus-like particles reveals structural dissimilarities between different forms of E2. Journal of General Virology. 2001;82(pt. 8):1877–1883.Owsianka A., Clayton R. F., Loomis-Price L.D., McKeating J.A., Patel A. H. Functional analysis of hepatitis C virus E2 glycoproteins and virus-like particles reveals structural dissimilarities between different forms of E2 // J. Gen. Virol. 2001. Vol. 82, pt. 8. P. 1877–1883.