Anti-HBc mirrors the activation of HBV-specific CD8+ T cell immune response and exhibits a direct effect on HBV control

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY Antiviral research Pub Date : 2024-07-31 DOI:10.1016/j.antiviral.2024.105975

Guofu Ye , Chengcong Chen , Yongjun Zhou , Libo Tang , Jianzhong Cai , Yiyan Huang , Jiayue Yang , Yaoting Feng , Liangxing Chen , Yuhao Wang , Yanchen Ma , Guanfeng Lin , Yingsong Wu , Xiaotao Jiang , Jinlin Hou , Yongyin Li

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Abstract

Background

Hepatitis B core antibody (anti-HBc) is commonly present in patients with chronic hepatitis B virus (HBV) infection and serves as a marker of humoral immunity. Herein, we aim to investigate the correlation between anti-HBc and antiviral immune response and its putative role in HBV control.

Methods

Quantitative anti-HBc and levels of anti-HBc subtypes were measured in chronic hepatitis B (CHB) patients. The effects of anti-HBc on immune cells and HBV replication were evaluated using the HBV mouse models and human hepatoma cell lines.

Results

Baseline levels of IgG1 and IgG3 anti-HBc were elevated in CHB patients with favorable treatment response, and correlated with the virological response observed at week 52. Additionally, increased levels of IgM and IgG1 anti-HBc were observed exclusively in CHB patients with liver inflammation. Notably, significant correlations were identified between quantitative levels of anti-HBc and the frequencies of HBcAg-specific CD8⁺ T cells. Intriguingly, HBcAg efficiently activates T cells aided by B cells in vitro experiments. Moreover, anti-HBc inhibits HBV replication either by a direct effect or through complement-mediated cytotoxicity in HBV-producing cell lines.

Conclusions

Anti-HBc reflects the activation of an HBV-specific CD8⁺ T cell immune response and may have anti-HBV activity.

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抗 HBc 可反映 HBV 特异性 CD8+ T 细胞免疫反应的激活，并对 HBV 控制产生直接影响。

背景：乙型肝炎核心抗体（抗-HBc）常见于慢性乙型肝炎病毒（HBV）感染患者，是体液免疫的标志物。在此，我们旨在研究抗 HBc 与抗病毒免疫反应之间的相关性及其在 HBV 控制中的作用：方法：测定慢性乙型肝炎（CHB）患者的抗 HBc 定量和抗 HBc 亚型水平。使用 HBV 小鼠模型和人类肝癌细胞系评估了抗 HBc 对免疫细胞和 HBV 复制的影响：结果：治疗反应良好的慢性乙型肝炎患者的 IgG1 和 IgG3 抗 HBc 基线水平升高，并与第 52 周观察到的病毒学反应相关。此外，IgM 和 IgG1 抗 HBc 水平的升高只出现在有肝脏炎症的慢性乙型肝炎患者中。值得注意的是，抗 HBc 的定量水平与 HBcAg 特异性 CD8+ T 细胞的频率之间存在明显的相关性。耐人寻味的是，在体外实验中，HBcAg 能在 B 细胞的帮助下有效激活 T 细胞。此外，抗 HBc 可通过直接作用或补体介导的细胞毒性抑制 HBV 生产细胞系中的 HBV 复制：结论：抗 HBc 反映了 HBV 特异性 CD8+ T 细胞免疫反应的激活，可能具有抗 HBV 活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.