清除HCV的免疫机制研究进展

肝脏 ›› 2024, Vol. 29 ›› Issue (11): 1301-1304.

清除HCV的免疫机制研究进展

马翠玲, 饶慧瑛

100044 北京大学人民医院感染与肝病中心,北京大学肝病研究所

收稿日期:2024-11-10 出版日期:2024-11-30 发布日期:2025-01-10

Received:2024-11-10 Online:2024-11-30 Published:2025-01-10

摘要/Abstract

摘要： HCV感染一直是世界性公共卫生难题,尽管治疗慢性HCV感染已经取得很大的突破,但HCV感染的隐匿性导致药物治疗人群十分有限,攻克HCV仍需要有效的疫苗。既往研究表明,强大而持久的HCV特异性CD8⁺ T细胞反应是介导HCV清除的主要免疫因素,CD4⁺ T细胞在其中起着重要的辅助作用。近年来研究发现,B细胞产生的中和抗体在清除HCV中也起着重要作用,但对于T细胞和B细胞如何协同发挥作用的研究仍然十分有限。本文综述了清除HCV感染的先天性及适应性免疫机制,以及体液免疫及细胞免疫的联合机制,并概述了目前病毒发生免疫逃避的主要机制。

马翠玲, 饶慧瑛. 清除HCV的免疫机制研究进展[J]. 肝脏, 2024, 29(11): 1301-1304.

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参考文献

[1] Bukh J. The history of hepatitis C virus (HCV): Basic research reveals unique features in phylogeny, evolution and the viral life cycle with new perspectives for epidemic control[J]. J Hepatol, 2016, 65(1 Suppl): S2-S21.
[2] Tsukiyama-Kohara K, Kohara M. Hepatitis C virus: Viral quasispecies and genotypes[J]. Int J Mol Sci, 2017, 19(1): 23.
[3] 中华医学会肝病学分会,中华医学会感染病学分会. 丙型肝炎防治指南(2022年版)[J]. 中华肝脏病杂志,2023,30(12): 1332-1348.
[4] Barik S. Suppression of innate immunity by the hepatitis C virus (HCV): Revisiting the specificity of host-virus interactive pathways[J]. Int J Mol Sci, 2023, 24(22): 16100.
[5] Yoon J C, Yang C M, Song Y, et al. Natural killer cells in hepatitis C: current progress[J]. World J Gastroenterol, 2016, 22(4): 1449.
[6] Osburn W O, Snider A E, Wells B L, et al. Clearance of hepatitis C infection is associated with the early appearance of broad neutralizing antibody responses[J]. Hepatology, 2014, 59(6): 2140-2151.
[7] Kinchen V J, Zahid M N, Flyak A I, et al. Broadly neutralizing antibody mediated clearance of human hepatitis C virus infection[J]. Cell Host & Microbe, 2018, 24(5): 717-730.e5.
[8] Frumento N, Sinnis-Bourozikas A, Paul H T, et al. Neutralizing antibodies evolve to exploit vulnerable sites in the HCV envelope glycoprotein E2 and mediate spontaneous clearance of infection[J]. Immunity, 2024, 57(1): 40-51.e5.
[9] Merat S J, Bru C, Van De Berg D, et al. Cross-genotype AR3-specific neutralizing antibodies confer long-term protection in injecting drug users after HCV clearance[J]. J Hepatol, 2019, 71(1): 14-24.
[10] Baktash Y, Madhav A, Coller K E, et al. Single particle imaging of polarized hepatoma organoids upon hepatitis C virus infection reveals an ordered and sequential entry process[J]. Cell Host Microbe, 2018, 23(3): 382-394.e5.
[11] Jo J, Aichele U, Kersting N, et al. Analysis of CD8⁺ T-cell-mediated inhibition of hepatitis C virus replication using a novel immunological model[J]. Gastroenterology, 2009, 136(4): 1391-1401.
[12] Hou H, Kang Y, Zeng Y, et al. Interleukin-7 augments CD8⁺ T cells function and promotes viral clearance in chronic hepatitis C virus infection[J]. Cytokine, 2018, 102: 26-33.
[13] Moreno-Cubero E, Larrubia J R. Specific CD8(+) T cell response immunotherapy for hepatocellular carcinoma and viral hepatitis[J]. World J Gastroenterol, 2016, 22(28): 6469-6483.
[14] Smith S, Honegger J R, Walker C. T-cell immunity against the hepatitis C virus: A persistent research priority in an era of highly effective therapy[J]. Cold Spring Harb Perspect Med, 2021, 11(1): a036954.
[15] Zhai N, Chi X, Li T, et al. Hepatitis C virus core protein triggers expansion and activation of CD4(+)CD25(+) regulatory T cells in chronic hepatitis C patients[J]. Cell Mol Immunol, 2015, 12(6): 743-749.
[16] Chen D Y, Wolski D, Aneja J, et al. Hepatitis C virus-specific CD4⁺ T cell phenotype and function in different infection outcomes[J]. J Clin Invest, 2020, 130(2): 768-773.
[17] Osburn W O, Fisher B E, Dowd K A, et al. Spontaneous control of primary hepatitis C virus infection and immunity against persistent reinfection[J]. Gastroenterology, 2010, 138(1): 315-324.
[18] Abdel-Hakeem M S, Bédard N, Murphy D, et al. Signatures of protective memory immune responses during hepatitis C virus reinfection[J]. Gastroenterology, 2014, 147(4): 870-881.e8.
[19] Page K, Melia M T, Veenhuis R T, et al. Randomized trial of a vaccine regimen to prevent chronic HCV infection[J]. New Engl J Med, 2021, 384(6): 541-549.
[20] Gridley J, Holland B, Salinas E, et al. Concerted synergy between viral-specific IgG and CD8⁺ T cells is critical for clearance of an HCV-related rodent hepacivirus[J]. Hepatology, 2024, 80(4): 937-950.
[21] Salinas E, Boisvert M, Upadhyay A A, et al. Early T follicular helper cell activity accelerates hepatitis C virus-specific B cell expansion[J]. J Clin Invest, 2021, 131(2): e140590.
[22] Eisa M, Gomez-Escobar E, Bédard N, et al. Coordinated expansion of memory T follicular helper and B cells mediates spontaneous clearance of HCV reinfection[J]. Front Immunol, 2024, 15: 1403769.
[23] Chigbu D I, Loonawat R, Sehgal M, et al. Hepatitis C virus infection: host virus interaction and mechanisms of viral persistence[J]. Cells, 2019, 8(4): 376.
[24] Frumento N, Flyak A I, Bailey J R. Mechanisms of HCV resistance to broadly neutralizing antibodies[J]. Curr Opin Virol, 2021, 50: 23-29.