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Hepatitis C Virus Nonstructural Protein 3 Increases Secretion of Interleukin-1beta in HEK293T Cells with a Reconstructed NLRP3 Inflammasome

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Abstract—The pathology of diseases arising from infections by viruses of Flaviviridae is largely determined by the development of systemic inflammation. The cytokines interleukin-1beta and interleukin-18 play a key role in triggering inflammation. Their secretion from cells, in its turn, is induced upon activation of inflammasomes. Activation of NLRP3 (NLR pyrin domain-containing family 3) inflammasomes was detected in cells infected with Flaviviridae. Some nonstructural proteins of these viruses have been shown to be able to activate or to inhibit the NLRP3 inflammasome, in particular, through interaction with its components. In this study, a functional NLRP3 inflammasome was reconstructed in human HEK293T cells and the effect of some nonstructural proteins of individual Flaviviridae viruses on it was studied. This model did not reveal any impact of nonstructural NS1 proteins of the West Nile virus, NS3 of hepatitis C virus, or NS5 of tick-borne encephalitis virus on the inflammasome components content. At the same time, in the presence of the NS1 of the West Nile virus and NS5 of the tick-borne encephalitis virus, the level of secretion of interleukin-1beta did not change, whereas in the presence of the NS3 protein of the hepatitis C virus, it increased by 1.5 times. Thus, NS3 can be considered as one of the factors of NLRP3 inflammasome activation and inflammatory pathogenesis in chronic hepatitis C virus infection.

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REFERENCES

  1. Franchi L., Warner N., Viani K., Nunez G. 2009. Function of Nod-like receptors in microbial recognition and host defense. Immunol. Rev. 227, 106‒128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Yang Y., Wang H., Kouadir M., Song H., Shi F. 2019. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Disease. 10, 128.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lu A., Li Y., Schmidt F.I., Yin Q., Chen S., Fu T.M., Tong A.B., Ploegh H.L., Mao Y., Wu H. 2016. Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism. Nat. Struct. Mol. Biol. 23, 416‒425.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Malik A., Kanneganti T.D. 2017. Inflammasome activation and assembly at a glance. J. Cell Sci. 130, 3955‒3963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Swanson K.V., Deng M., Ting J.P. 2019. The NLRP3 inflammasome: Molecular activation and regulation to therapeutics. Nat. Rev. Immunol. 19, 477‒489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gram A.M., Frenkel J., Ressing M.E. 2012. Inflammasomes and viruses: Cellular defence versus viral offence. J. Gen. Virol. 93, 2063‒2075.

    Article  CAS  PubMed  Google Scholar 

  7. Cai X., Chen J., Xu H., Liu S., Jiang Q.X., Halfmann R., Chen Z.J. 2014. Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. Cell. 156, 1207‒1222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Broz P., Dixit V.M. 2016. Inflammasomes: Mechanism of assembly, regulation and signalling. Nat. Rev. Immunol. 16, 407‒420.

    Article  CAS  PubMed  Google Scholar 

  9. Mangan M.S.J., Olhava E.J., Roush W.R., Seidel H.M., Glick G.D., Latz E. 2018. Targeting the NLRP3 inflammasome in inflammatory diseases. Nat. Rev. Drug Discovery. 17, 688.

    Article  CAS  PubMed  Google Scholar 

  10. Rathinam V.A., Fitzgerald K.A. 2016. Inflammasome complexes: Emerging mechanisms and effector functions. Cell. 165, 792‒800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. He W.T., Wan H., Hu L., Chen P., Wang X., Huang Z., Yang Z.H., Zhong C.Q., Han J. 2015. Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion. Cell. Res. 25, 1285‒1298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shi J., Zhao Y., Wang K., Shi X., Wang Y., Huang H., Zhuang Y., Cai T., Wang F., Shao F. 2015. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 526, 660‒665.

    Article  CAS  PubMed  Google Scholar 

  13. Dinarello C.A., Novick D., Kim S., Kaplanski G. 2013. Interleukin-18 and IL-18 binding protein. Front. Immunol. 4, 289.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Joosten L.A., Netea M.G., Dinarello C.A. 2013. Interleukin-1beta in innate inflammation, autophagy and immunity. Semin. Immunol. 25, 416‒424.

    Article  CAS  PubMed  Google Scholar 

  15. Bauernfeind F.G., Horvath G., Stutz A., Alnemri E.S., MacDonald K., Speert D., Fernandes-Alnemri T., Wu J., Monks B.G., Fitzgerald K.A., Hornung V., Latz E. 2009. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J. Immunol. 183, 787‒791.

    Article  CAS  PubMed  Google Scholar 

  16. Christgen S., Kanneganti T.D. 2020. Inflammasomes and the fine line between defense and disease. Curr. Opin. Immunol. 62, 39‒44.

    Article  CAS  PubMed  Google Scholar 

  17. Afonina I.S., Zhong Z., Karin M., Beyaert R. 2017. Limiting inflammation-the negative regulation of NF-kappaB and the NLRP3 inflammasome. Nat. Immunol. 18, 861‒869.

    Article  CAS  PubMed  Google Scholar 

  18. Lamkanfi M., Dixit V.M. 2014. Mechanisms and functions of inflammasomes. Cell. 157, 1013‒1022.

    Article  CAS  PubMed  Google Scholar 

  19. Zhao C., Zhao W. 2020. NLRP3 inflammasome-A key player in antiviral responses. Front. Immunol. 11, 211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Latanova A., Starodubova E., Karpov V. 2022. Flaviviridae nonstructural proteins: The role in molecular mechanisms of triggering inflammation. Viruses. 14, 1808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. He Z., Chen J., Zhu X., An S., Dong X., Yu J., Zhang S., Wu Y., Li G., Zhang Y., Wu J., Li M. 2018. NLRP3 Inflammasome activation mediates Zika virus-associated inflammation. J. Infect. Dis. 217, 1942‒1951.

    Article  CAS  PubMed  Google Scholar 

  22. Wang W., Li G., De W., Luo Z., Pan P., Tian M., Wang Y., Xiao F., Li A., Wu K., Liu X., Rao L., Liu F., Liu Y., Wu J. 2018. Zika virus infection induces host inflammatory responses by facilitating NLRP3 inflammasome assembly and interleukin-1beta secretion. Nat. Commun. 9, 106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zheng Y., Liu Q., Wu Y., Ma L., Zhang Z., Liu T., Jin S., She Y., Li Y.P., Cui J. 2018. Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS1-caspase-1 axis. EMBO J. 37, e99347.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Gim E., Shim D.W., Hwang I., Shin O.S., Yu J.W. 2019. Zika virus impairs host NLRP3-mediated inflammasome activation in an NS3-dependent manner. Immune Network. 19, e40.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shrivastava G., Visoso-Carvajal G., Garcia-Cordero J., Leon-Juarez M., Chavez-Munguia B., Lopez T., Nava P., Villegas-Sepulveda N., Cedillo-Barron L. 2020. Dengue virus serotype 2 and its non-structural proteins 2A and 2B activate NLRP3 inflammasome. Front. Immunol. 11, 352.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ramos H.J., Lanteri M.C., Blahnik G., Negash A., Suthar M.S., Brassil M.M., Sodhi K., Treuting P.M., Busch M.P., Norris P.J., Gale M., Jr. 2012. IL-1beta signaling promotes CNS-intrinsic immune control of West Nile virus infection. PLoS Pathog. 8, e1003039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chen W., Xu Y., Li H., Tao W., Xiang Y., Huang B., Niu J., Zhong J., Meng G. 2014. HCV genomic RNA activates the NLRP3 inflammasome in human myeloid cells. PLoS One. 9, e84953.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Negash A.A., Ramos H.J., Crochet N., Lau D.T., Doehle B., Papic N., Delker D.A., Jo J., Bertoletti A., Hagedorn C.H., Gale M., Jr. 2013. IL-1beta production through the NLRP3 inflammasome by hepatic macrophages links hepatitis C virus infection with liver inflammation and disease. PLoS Pathog. 9, e1003330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shrivastava S., Mukherjee A., Ray R., Ray R.B. 2013. Hepatitis C virus induces interleukin-1beta (IL-1beta)/IL-18 in circulatory and resident liver macrophages. J. Virol. 87, 12284‒12290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Atrasheuskaya A.V., Fredeking T.M., Ignatyev G.M. 2003. Changes in immune parameters and their correction in human cases of tick-borne encephalitis. Clin. Exp. Immunol. 131, 148‒154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Isaguliants M.G., Petrakova N.V., Mokhonov V.V., Pokrovskaya K., Suzdaltzeva Y.G., Krivonos A.V., Zaberezhny A.D., Garaev M.M., Smirnov V.D., Nordenfelt E. 2003. DNA immunization efficiently targets conserved functional domains of protease and A-TPase/helicase of nonstructural 3 protein (NS3) of human hepatitis C virus. Immunol. Lett. 88, 1‒13.

    Article  CAS  PubMed  Google Scholar 

  32. Shi C.S., Nabar N.R., Huang N.N., Kehrl J.H. 2019. SARS-coronavirus open reading frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes. Cell Death Discovery 5, 101.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Chuang Y.T., Lin Y.C., Lin K.H., Chou T.F., Kuo W.C., Yang K.T., Wu P.R., Chen R.H., Kimchi A., Lai M.Z. 2011. Tumor suppressor death-associated protein kinase is required for full IL-1beta production. Blood. 117, 960‒970.

    Article  CAS  PubMed  Google Scholar 

  34. Ito S., Hara Y., Kubota T. 2014. CARD8 is a negative regulator for NLRP3 inflammasome, but mutant NLRP3 in cryopyrin-associated periodic syndromes escapes the restriction. Arthritis Res. Ther. 16, R52.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Mao L., Kitani A., Hiejima E., Montgomery-Recht K., Zhou W., Fuss I., Wiestner A., Strober W. 2020. Bruton tyrosine kinase deficiency augments NLRP3 inflammasome activation and causes IL-1beta-mediated colitis. J. Clin. Invest. 130, 1793‒1807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zito G., Buscetta M., Cimino M., Dino P., Bucchieri F., Cipollina C. 2020. Cellular models and assays to study NLRP3 inflammasome biology. Int. J. Mol. Sci. 21, 4294.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Coll R.C., Hill J.R., Day C.J., Zamoshnikova A., Boucher D., Massey N.L., Chitty J.L., Fraser J.A., Jennings M.P., Robertson A.A.B., Schroder K. 2019. MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition. Nat. Chem. Biol. 15, 556‒559.

    Article  CAS  PubMed  Google Scholar 

  38. Hafner-Bratkovic I., Susjan P., Lainscek D., Tapia-Abellan A., Cerovic K., Kadunc L., Angosto-Bazarra D., Pelegrin P., Jerala R. 2018. NLRP3 lacking the leucine-rich repeat domain can be fully activated via the canonical inflammasome pathway. Nat. Commun. 9, 5182.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Vande Walle L., Stowe I.B., Sacha P., Lee B.L., Dem-on D., Fossoul A., Van Hauwermeiren F., Saavedra P.H.V., Simon P., Subrt V., Kostka L., Stivala C.E., Pham V.C., Staben S.T., Yamazoe S., Konvalinka J., Kayagaki N., Lamkanfi M. 2019. MCC950/CRID3 potently targets the NACHT domain of wild-type NLRP3 but not disease-associated mutants for inflammasome inhibition. PLoS Biol. 17, e3000354.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Wang W., Xiao F., Wan P., Pan P., Zhang Y., Liu F., Wu K., Liu Y., Wu J. 2017. EV71 3D protein binds with NLRP3 and enhances the assembly of inflammasome complex. PLoS Pathog. 13, e1006123.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Guffanti A.A., Davidson L.F., Mann T.M., Krulwich T.A. 1979. Nigericin-induced death of an acidophilic bacterium. J. Gen. Microbiol. 114, 201–206.

    Article  CAS  PubMed  Google Scholar 

  42. Eytan G.D., Carlenor E., Rydstrom J. 1990. Energy-linked transhydrogenase. Effects of valinomycin and nigericin on the ATP-driven transhydrogenase reaction catalyzed by reconstituted transhydrogenase-ATPase vesicles. J. Biol. Chem. 265, 12949‒12954.

    Article  CAS  PubMed  Google Scholar 

  43. Kongkaneramit L., Sarisuta N., Azad N., Lu Y., Iyer A.K., Wang L., Rojanasakul Y. 2008. Dependence of reactive oxygen species and FLICE inhibitory protein on lipofectamine-induced apoptosis in human lung epithelial cells. J. Pharmacol. Exp. Ther. 325, 969‒977.

    Article  CAS  PubMed  Google Scholar 

  44. Mo R.H., Zaro J.L., Ou J.H., Shen W.C. 2012. Effects of lipofectamine 2000/siRNA complexes on autophagy in hepatoma cells. Mol. Biotechnol. 51, 1‒8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Napoli E., Liu S., Marsilio I., Zarbalis K., Giulivi C. 2017. Lipid-based DNA/siRNA transfection agents disrupt neuronal bioenergetics and mitophagy. Biochem. J. 474, 3887‒3902.

    Article  CAS  PubMed  Google Scholar 

  46. He J., Li T., Prochnicki T., Horvath G., Latz E., Takeoka S. 2019. Membrane fusogenic lysine type lipid assemblies possess enhanced NLRP3 inflammasome activation potency. Biochem. Biophys. Rep. 18, 100623.

    PubMed  PubMed Central  Google Scholar 

  47. Li T., He J., Horvath G., Prochnicki T., Latz E., Takeoka S. 2018. Lysine-containing cationic liposomes activate the NLRP3 inflammasome: Effect of a spacer between the head group and the hydrophobic moieties of the lipids. Nanomed.: Nanotechnol. Biol. Med. 14, 279‒288.

    Article  CAS  Google Scholar 

  48. Zhong Z., Zhai Y., Liang S., Mori Y., Han R., Sutterwala F.S., Qiao L. 2013. TRPM2 links oxidative stress to NLRP3 inflammasome activation. Nat. Commun. 4, 1611.

    Article  PubMed  Google Scholar 

  49. Elrefaey A.M.E., Hollinghurst P., Reitmayer C.M., Alphey L., Maringer K. 2021. Innate immune antagonism of mosquito-borne flaviviruses in humans and mosquitoes. Viruses. 13, 2116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Negash A.A., Olson R.M., Griffin S., Gale M., Jr. 2019. Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation. PLoS Pathog. 15, e1007593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Chang S., Dolganiuc A., Szabo G. 2007. Toll-like receptors 1 and 6 are involved in TLR2-mediated macrophage activation by hepatitis C virus core and NS3 proteins. J. Leukocyte Biol. 82, 479‒487.

    Article  CAS  PubMed  Google Scholar 

  52. Dolganiuc A., Kodys K., Kopasz A., Marshall C., Do T., Romics L., Jr., Mandrekar P., Zapp M., Szabo G. 2003. Hepatitis C virus core and nonstructural protein 3 proteins induce pro- and anti-inflammatory cytokines and inhibit dendritic cell differentiation. J. Immunol. 170, 5615‒5624.

    Article  CAS  PubMed  Google Scholar 

  53. Rajalakshmy A.R., Malathi J., Madhavan H.N. 2015. Hepatitis C virus NS3 mediated microglial inflammation via TLR2/TLR6 MyD88/NF-kappaB pathway and Toll like receptor ligand treatment furnished immune tolerance. PLoS One. 10, e0125419.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Rajalakshmy A.R., Malathi J., Madhavan H.N. 2014. HCV core and NS3 proteins mediate toll like receptor induced innate immune response in corneal epithelium. Exp. Eye Res. 128, 117–128.

    Article  CAS  PubMed  Google Scholar 

  55. Martinez-Esparza M., Tristan-Manzano M., Ruiz-Alcaraz A.J., Garcia-Penarrubia P. 2015. Inflammatory status in human hepatic cirrhosis. World J. Gastroenterol. 21, 11522‒11541.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Chattergoon M.A., Levine J.S., Latanich R., Osburn W.O., Thomas D.L., Cox A.L. 2011. High plasma interleukin-18 levels mark the acute phase of hepatitis C virus infection. J. Infect. Dis. 204, 1730‒1740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Vecchiet J., Falasca K., Cacciatore P., Zingariello P., Dalessandro M., Marinopiccoli M., D’Amico E., Palazzi C., Petrarca C., Conti P., Pizzigallo E., Guagnano M.T. 2005. Association between plasma interleukin-18 levels and liver injury in chronic hepatitis C virus infection and non-alcoholic fatty liver disease. Ann. Clin. Lab. Sci. 35, 415‒422.

    CAS  PubMed  Google Scholar 

  58. Chattergoon M.A., Latanich R., Quinn J., Winter M.E., Buckheit R.W., 3rd, Blankson J.N., Pardoll D., Cox A.L. 2014. HIV and HCV activate the inflammasome in monocytes and macrophages via endosomal Toll-like receptors without induction of type 1 interferon. PLoS Pathog. 10, e1004082.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Ramachandran A., Kumar B., Waris G., Everly D. 2021. Deubiquitination and activation of the NLRP3 inflammasome by UCHL5 in HCV-infected cells. Microbiol. Spectrum. 9, e0075521.

    Article  Google Scholar 

  60. Farquhar M.J., McKeating J.A. 2008. Primary hepatocytes as targets for hepatitis C virus replication. J. Viral. Hepatitis. 15, 849‒854.

    Article  CAS  Google Scholar 

  61. Bureau C., Bernad J., Chaouche N., Orfila C., Beraud M., Gonindard C., Alric L., Vinel J.P., Pipy B. 2001. Nonstructural 3 protein of hepatitis C virus triggers an oxidative burst in human monocytes via activation of NADPH oxidase. J. Biol. Chem. 276, 23077‒23083.

    Article  CAS  PubMed  Google Scholar 

  62. Pal S., Polyak S.J., Bano N., Qiu W.C., Carithers R.L., Shuhart M., Gretch D.R., Das A. 2010. Hepatitis C virus induces oxidative stress, DNA damage and modulates the DNA repair enzyme NEIL1. J. Gastroenterol. Hepatol. 25, 627‒634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Shah R., Ahovegbe L., Niebel M., Shepherd J., Thomson E.C. 2021. Non-epidemic HCV genotypes in low- and middle-income countries and the risk of resistance to current direct-acting antiviral regimens. J. Hepatol. 75, 462‒473.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Polaris Observatory H.C.V.C. 2017. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: A modelling study. Lancet. Gastroenterol. Hepatol. 2, 161‒176.

    Article  Google Scholar 

  65. Webster G., Barnes E., Brown D., Dusheiko G. 2000. HCV genotypes‒role in pathogenesis of disease and response to therapy. Baillieres Best Pract. Res. Clin. Gastroenterol. 14, 229‒240.

    Article  CAS  PubMed  Google Scholar 

  66. Liu G., Cai Q., Li Z., Shao X., Luo Q., Zhang X., Zhao Z. 2016. Effect of drug resistance mutations on antiviral agents in HCV patients. Antiviral Ther. 21, 369‒375.

    Article  CAS  Google Scholar 

  67. Petruzziello A., Marigliano S., Loquercio G., Cozzolino A., Cacciapuoti C. 2016. Global epidemiology of hepatitis C virus infection: An up-date of the distribution and circulation of hepatitis C virus genotypes. World J. Gastroenterol. 22, 7824‒7840.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Irshad M., Mankotia D.S., Irshad K. 2013. An insight into the diagnosis and pathogenesis of hepatitis C virus infection. World J. Gastroenterol. 19, 7896‒7909.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Yamane D., McGivern D.R., Masaki T., Lemon S.M. 2013. Liver injury and disease pathogenesis in chronic hepatitis C. Curr. Topics Microbiol. Immunol. 369, 263‒288.

    CAS  Google Scholar 

  70. Mondelli M.U., Silini E. 1999. Clinical significance of hepatitis C virus genotypes. J. Hepatol. 31 (suppl. 1), 65‒70.

    Article  PubMed  Google Scholar 

  71. Lanciotti R.S., Lambert A.J., Holodniy M., Saavedra S., Signor Ldel C. 2016. Phylogeny of Zika virus in Western Hemisphere, 2015. Emerging Infect. Dis. 22, 933‒935.

    Article  Google Scholar 

  72. Shao Q., Herrlinger S., Zhu Y.N., Yang M., Goodfellow F., Stice S.L., Qi X.P., Brindley M.A., Chen J.F. 2017. The African Zika virus MR-766 is more virulent and causes more severe brain damage than current Asian lineage and dengue virus. Development. 144, 4114‒4124.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Dowall S.D., Graham V.A., Hewson R. 2020. Lineage-dependent differences of Zika virus infection in a susceptible mouse model are associated with different profiles of cytokines, chemokines, growth factors and acute phase proteins. Cytokine. 125, 154864.

    Article  CAS  PubMed  Google Scholar 

  74. Mundim A., de Castro F.O.F., Albuquerque M.B.B., Vilanova-Costa C., Pfrimer I.A.H., Silva A. 2020. Major mutations in the NS3 gene region of hepatitis C virus related to the resistance to direct acting antiviral drugs: A systematic review. Virus. Dis. 31, 220‒228.

    CAS  Google Scholar 

  75. Sagnelli E., Starace M., Minichini C., Pisaturo M., Macera M., Sagnelli C., Coppola N. 2018. Resistance detection and re-treatment options in hepatitis C virus-related chronic liver diseases after DAA-treatment failure. Infection. 46, 761‒783.

    Article  PubMed  Google Scholar 

  76. Lanini S., Scognamiglio P., Mecozzi A., Lombardozzi L., Vullo V., Angelico M., Gasbarrini A., Taliani G., Attili A.F., Perno C.F., De Santis A., Puro V., Cerqua F., D’Offizi G., Pellicelli A., Armignacco O., Mennini F.S., Siciliano M., Girardi E., Panella V., Ippolito G., members of the Lazio Region H.C.V.t.g. 2018. Impact of new DAA therapy on real clinical practice: A multicenter region-wide cohort study. BMC Infect. Dis. 18, 223.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Bradshaw D., Mbisa J.L., Geretti A.M., Healy B.J., Cooke G.S., Foster G.R., Thomson E.C., McLauchlan J., Agarwal K., Sabin C., Mutimer D., Moss P., Irving W.L., Barnes E., Hepatitis C Trust U.K. 2019. Consensus recommendations for resistance testing in the management of chronic hepatitis C virus infection: Public Health England HCV Resistance Group. J. Infect. 79, 503‒512.

    Article  PubMed  Google Scholar 

  78. Costa V.D., Pellegrini P., Rotman V., Pittella A.M., Nunes E.P., Lago B.V., Lampe E., Mello F.C.A. 2019. Resistance mutations A30K and Y93N associated with treatment failure with sofosbuvir and daclatasvir for hepatitis C virus infection non-responder patients: case reports. Viruses. 11, 1004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Sarrazin C. 2021. Treatment failure with DAA therapy: Importance of resistance. J. Hepatol. 74, 1472‒1482.

    Article  CAS  PubMed  Google Scholar 

  80. Paolucci S., Novazzi F., Piralla A., Maserati R., Gulminetti R., Novati S., Barbarini G., Sacchi P., Fratini A., Bellotti L., Baldanti F. 2019. Viral dynamics among HCV infected patients with different genotypes treated with genotypic specific or pan-genotypic direct-acting antiviral agent combinations. Infect. Drug Resist. 12, 1975‒1984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Schwerk J., Negash A., Savan R., Gale M., Jr. 2021. Innate immunity in hepatitis C virus infection. Cold Spring Harb. Perspect. Med. 11, a036988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Welsch C., Efinger M., von Wagner M., Herrmann E., Zeuzem S., Welzel T.M., Lange C.M. 2017. Ongoing liver inflammation in patients with chronic hepatitis C and sustained virological response. PLoS One. 12, e0171755.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by the Russian Science Foundation (grant no. 21-74-00124).

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    A. A. Latanova, E. S. Starodubova & V. L. Karpov

  2. Сhumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products (Institute of Poliomyelitis), Russian Academy of Sciences, 108811, Moscow, Russia

    K. K. Tuchinskaya

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  1. A. A. Latanova
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  3. E. S. Starodubova
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Correspondence to A. A. Latanova.

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Abbreviations: ASC, Apoptosis-associated speck-like protein containing a CARD; DAMP, Damage-associated molecular pattern; IQR, Interquartile range; NLRP3, NLR family pyrin domain-containing 3; NS1, NS3, NS5, Nonstructural proteins 1, 3, 5; PAMP, Pathogen-associated molecular pattern; TLR, Toll-like receptor; HCV, hepatitis C virus; WNV, West Nile virus; TBEV, tick-borne encephalitis virus; IL-1beta, interleukin-1beta; ELISA, enzyme immunoassay; IFN, interferon; PAAG, polyacrylamide gel; TNF-alpha, tumor necrosis factor alpha.

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Latanova, A.A., Tuchinskaya, K.K., Starodubova, E.S. et al. Hepatitis C Virus Nonstructural Protein 3 Increases Secretion of Interleukin-1beta in HEK293T Cells with a Reconstructed NLRP3 Inflammasome. Mol Biol 57, 876–884 (2023). https://doi.org/10.1134/S0026893323050084

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