Hepatitis C virus-specific immune responses following direct-acting antivirals administered during recent hepatitis C virus infection.
direct-acting antivirals
hepatitis C virus
immune exhaustion
immune restoration
protective immunity
Journal
Journal of viral hepatitis
ISSN: 1365-2893
Titre abrégé: J Viral Hepat
Pays: England
ID NLM: 9435672
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
12
10
2022
accepted:
13
10
2022
pubmed:
28
10
2022
medline:
23
12
2022
entrez:
27
10
2022
Statut:
ppublish
Résumé
Individuals who spontaneously clear hepatitis C virus (HCV) infection have demonstrated evidence of partial protective immunity, whereas treatment-induced clearance provides little or no protection against reinfection. We aimed to investigate whether treatment of acute HCV infection with direct-acting antivirals (DAA) prevents establishment of, or reverses, T-cell exhaustion, leading to a virus-specific T-cell immune profile more similar to that seen in spontaneous clearance. The magnitude and breadth of HCV-specific T-cell responses before and after DAA or interferon-based therapy in acute or chronic HCV were compared to those of participants with spontaneous clearance of infection, using Enzyme-linked Immunospot (ELISPOT). PBMCs were available for 55 patients comprising 4 groups: spontaneous clearance (n = 17), acute interferon (n = 14), acute DAA (n = 13) and chronic DAA (n = 11). After controlling for sex, the magnitude of post-treatment HCV-specific responses after acute DAA treatment was greater than after chronic DAA or acute IFN treatment and similar to those found in spontaneous clearers. However, spontaneous clearers responded to more HCV peptide pools indicating greater breadth of response. In conclusion, early treatment with DAAs may prevent or reverse some degree of immune exhaustion and result in stronger HCV-specific responses post-treatment. However, individuals with spontaneous clearance had broader HCV-specific responses.
Substances chimiques
Antiviral Agents
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
64-72Informations de copyright
© 2022 John Wiley & Sons Ltd.
Références
Organization, W.H. Global progress report on HIV, viral hepatitis and sexually transmitted infections. 2021.
Hoofnagle JH. Course and outcome of hepatitis C. Hepatology. 2002;36:S21-S29. doi:10.1053/jhep.2002.36227
Islam N, Krajden M, Shoveller J, et al. Hepatitis C cross-genotype immunity and implications for vaccine development. Sci Rep. 2017;7:12326. doi:10.1038/s41598-017-10190-8
Shoukry NH, Grakoui A, Houghton M, et al. Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection. J Exp Med. 2003;197:1645-1655. doi:10.1084/jem.20030239
Osburn WO, Fisher BE, Dowd KA, et al. Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection. Gastroenterology. 2010;138:315-324. doi:10.1053/j.gastro.2009.09.017
Abdel-Hakeem MS, Bédard N, Murphy D, Bruneau J, Shoukry NH. Signatures of protective memory immune responses during hepatitis C virus reinfection. Gastroenterology. 2014;147:870-881.e878. doi:10.1053/j.gastro.2014.07.005
Mehta SH, Cox A, Hoover DR, et al. Protection against persistence of hepatitis C. Lancet. 2002;359:1478-1483. doi:10.1016/S0140-6736(02)08435-0
Prokunina-Olsson L, Muchmore B, Tang W, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet. 2013;45:164-171. doi:10.1038/ng.2521
Gruener NH, Lechner F, Jung MC, et al. Sustained dysfunction of antiviral CD8+ T lymphocytes after infection with hepatitis C virus. J Virol. 2001;75:5550-5558. doi:10.1128/JVI.75.12.5550-5558.2001
Shin EC, Sung PS, Park SH. Immune responses and immunopathology in acute and chronic viral hepatitis. Nat Rev Immunol. 2016;16:509-523. doi:10.1038/nri.2016.69
Wherry EJ, Blattman JN, Murali-Krishna K, van der Most R, Ahmed R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol. 2003;77:4911-4927.
Penna A, Pilli M, Zerbini A, et al. Dysfunction and functional restoration of HCV-specific CD8 responses in chronic hepatitis C virus infection. Hepatology. 2007;45:588-601. doi:10.1002/hep.21541
Golden-Mason L, Palmer B, Klarquist J, Mengshol JA, Castelblanco N, Rosen HR. Upregulation of PD-1 expression on circulating and intrahepatic hepatitis C virus-specific CD8+ T cells associated with reversible immune dysfunction. J Virol. 2007;81:9249-9258. doi:10.1128/JVI.00409-07
Urbani S, Amadei B, Tola D, et al. PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion. J Virol. 2006;80:11398-11403. doi:10.1128/JVI.01177-06
Jin HT, Anderson AC, Tan WG, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci U S A. 2010;107:14733-14738. doi:10.1073/pnas.1009731107
Golden-Mason L, Palmer BE, Kassam N, et al. Negative immune regulator Tim-3 is overexpressed on T cells in hepatitis C virus infection and its blockade rescues dysfunctional CD4+ and CD8+ T cells. J Virol. 2009;83:9122-9130. doi:10.1128/JVI.00639-09
Golden-Mason L, Burton JR Jr, Castelblanco N, et al. Loss of IL-7 receptor alpha-chain (CD127) expression in acute HCV infection associated with viral persistence. Hepatology. 2006;44:1098-1109. doi:10.1002/hep.21365
Wherry EJ, Ha SJ, Kaech SM, et al. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity. 2007;27:670-684. doi:10.1016/j.immuni.2007.09.006
Abdel-Hakeem MS, Bedard N, Badr G, et al. Comparison of immune restoration in early versus late alpha interferon therapy against hepatitis C virus. J Virol. 2010;84:10429-10435. doi:10.1128/JVI.01094-10
Martin B, Hennecke N, Lohmann V, et al. Restoration of HCV-specific CD8+ T cell function by interferon-free therapy. J Hepatol. 2014;61:538-543. doi:10.1016/j.jhep.2014.05.043
Zhang C, Hua R, Cui Y, et al. Comprehensive mapping of antigen specific T cell responses in hepatitis C virus infected patients with or without spontaneous viral clearance. PLoS One. 2017;12:e0171217. doi:10.1371/journal.pone.0171217
Erickson S, Sangfelt O, Castro J, Heyman M, Einhorn S, Grander D. Interferon-alpha inhibits proliferation in human T lymphocytes by abrogation of interleukin 2-induced changes in cell cycle-regulatory proteins. Cell Growth Differ. 1999;10:575-582.
Hensel N, Gu Z, Sagar, et al. Memory-like HCV-specific CD8. Nat Immunol. 2021;22:229-239. doi:10.1038/s41590-020-00817-w
Martinello M, Gane E, Hellard M, et al. Sofosbuvir and ribavirin for 6 weeks is not effective among people with recent hepatitis C virus infection: The DARE-C II study. Hepatology. 2016;64:1911-1921. doi:10.1002/hep.28844
Martinello M, Hellard M, Shaw D, et al. Short duration response-guided treatment is effective for most individuals with recent hepatitis C infection: the ATAHC II and DARE-C I studies. Antivir Ther. 2016;21:465. doi:10.3851/IMP3073
Grebely J, Matthews GV, Hellard M, et al. Adherence to treatment for recently acquired hepatitis C virus (HCV) infection among injecting drug users. J Hepatol. 2011;55:76-85. doi:10.1016/j.jhep.2010.10.033
Dore GJ, Feld JJ, Thompson A, et al. Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial. J Hepatol. 2020;72:431-440. doi:10.1016/j.jhep.2019.10.010
Matthews GV, Bhagani S, Van der Valk M, et al. Sofosbuvir/velpatasvir for 12 vs. 6 weeks for the treatment of recently acquired hepatitis C infection. J Hepatol. 2021;75:829-839. doi:10.1016/j.jhep.2021.04.056
Nilsson C, Aboud S, Karlén K, Hejdeman B, Urassa W, Biberfeld G. Optimal blood mononuclear cell isolation procedures for gamma interferon enzyme-linked immunospot testing of healthy Swedish and Tanzanian subjects. Clin Vaccine Immunol. 2008;15:585-589. doi:10.1128/CVI.00161-07
Dore GJ, Hellard M, Matthews GV, et al. Effective treatment of injecting drug users with recently acquired hepatitis C virus infection. Gastroenterology. 2010;138:123-135.e121-122. doi:10.1053/j.gastro.2009.09.019
Grebely J, Raffa JD, Lai C, Krajden M, Conway B, Tyndall MW. Factors associated with spontaneous clearance of hepatitis C virus among illicit drug users. Can J Gastroenterol. 2007;21:447-451.
Mehrotra A, D'Angelo JA, Romney-Vanterpool A, et al. IFN-α suppresses myeloid cytokine production, impairing IL-12 production and the ability to support T-cell proliferation. J Infect Dis. 2020;222:148-157. doi:10.1093/infdis/jiaa064
Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399-401. doi:10.1038/nature08309
Bochud PY, Bibert S, Kutalik Z, et al. IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes. Hepatology. 2012;55:384-394. doi:10.1002/hep.24678
Thompson AJ, Muir AJ, Sulkowski MS, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology. 2010;139:120-129.e118. doi:10.1053/j.gastro.2010.04.013
Terczyńska-Dyla E, Bibert S, Duong FH, et al. Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes. Nat Commun. 2014;5:5699. doi:10.1038/ncomms6699
Jackowiak P, Kuls K, Budzko L, Mania A, Figlerowicz M. Phylogeny and molecular evolution of the hepatitis C virus. Infect Genet Evol. 2014;21:67-82. doi:10.1016/j.meegid.2013.10.021
Antonishyn NA, Ast VM, McDonald RR, et al. Rapid genotyping of hepatitis C virus by primer-specific extension analysis. J Clin Microbiol. 2005;43:5158-5163. doi:10.1128/JCM.43.10.5158-5163.2005