Hepatitis C virus (HCV) infection is a major worldwide problem with the highest incidence rates in Egypt. It affects B cells that serve as reservoirs for persistent HCV, resulting in phenotypic B cell alterations. Interleukin-7 (IL-7) is a cytokine with antiviral activity, important for B cell physiology. In addition, B cell-intrinsic toll-like receptor-7 (TLR7) signaling is required for optimal B cell responses during chronic viral infection, and the deficiency of TLR7 in B cells is sufficient to significantly impact antibody responses. Based on their known immunomodulatory effects, we hypothesized that direct-acting antiviral interferon-free therapy may affect TLR7 expression and the exhausted peripheral B cell compartment with the possibility of their restoration in patients who achieved a sustained virological response and their correlation to IL-7 level. This prospective study was accomplished on 80 Egyptian HCV patients and 75 controls. Frequencies of peripheral B cell subsets, TLR7 gene expression, TLR7 protein, and serum IL-7 levels were investigated by flow cytometry, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. B cell subpopulations were exhausted and partially restored among HCV patients after receiving treatment, but not recovered with regard to activated mature or resting memory B cells. Almost all responders to direct antiviral drugs showed upregulation of TLR7 gene expression and correlated with the frequency of memory B cell, but not with IL-7. Moreover, IL-7 was not significantly different between groups although correlated with immature transitional B cells. Results may indicate the interplay between TLR7 and B cells during remission or progression of HCV. Thus, TLR7 could be used as a promising biomarker for assessment of antiviral treatment efficacy among chronically infected HCV patients, and that targeting TLR7 may be used as a potential prophylactic and/or therapeutic agent during chronic HCV as well as immune-potentiation of memory B cells.

中文翻译：

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直接抗病毒无干扰素治疗期间慢性丙型肝炎病毒感染中记忆 B 细胞表型和 Toll 样受体 7 的调节：与白细胞介素 7 的相关性

丙型肝炎病毒 (HCV) 感染是一个主要的世界性问题，在埃及的发病率最高。它影响作为持久性 HCV 储存库的 B 细胞，导致表型 B 细胞改变。白细胞介素 7 (IL-7) 是一种具有抗病毒活性的细胞因子，对 B 细胞生理学很重要。此外，在慢性病毒感染期间，B 细胞内在的 toll 样受体 7 (TLR7) 信号传导是最佳 B 细胞反应所必需的，而 B 细胞中 TLR7 的缺乏足以显着影响抗体反应。基于它们已知的免疫调节作用，我们假设直接作用的无干扰素抗病毒治疗可能会影响 TLR7 表达和耗尽的外周 B 细胞区室，并有可能在获得持续病毒学应答的患者中恢复它们以及它们与 IL-7 水平的相关性。这项前瞻性研究是在 80 名埃及 HCV 患者和 75 名对照中完成的。分别通过流式细胞术、定量聚合酶链反应和酶联免疫吸附试验研究外周B细胞亚群的频率、TLR7基因表达、TLR7蛋白和血清IL-7水平。HCV 患者接受治疗后 B 细胞亚群耗尽并部分恢复，但活化的成熟或静息记忆 B 细胞未恢复。几乎所有直接抗病毒药物的应答者都表现出 TLR7 基因表达的上调，并且与记忆 B 细胞的频率相关，但与 IL-7 无关。此外，尽管与未成熟的移行 B 细胞相关，但 IL-7 组间没有显着差异。结果可能表明在 HCV 缓解或进展期间 TLR7 和 B 细胞之间的相互作用。因此，TLR7 可用作评估慢性感染 HCV 患者的抗病毒治疗效果的有前景的生物标志物，靶向 TLR7 可用作慢性 HCV 的潜在预防和/或治疗剂以及记忆 B 的免疫增强细胞。尽管与未成熟的移行 B 细胞相关，但 IL-7 组间没有显着差异。结果可能表明在 HCV 缓解或进展期间 TLR7 和 B 细胞之间的相互作用。因此，TLR7 可用作评估慢性感染 HCV 患者的抗病毒治疗效果的有前景的生物标志物，靶向 TLR7 可用作慢性 HCV 的潜在预防和/或治疗剂以及记忆 B 的免疫增强细胞。尽管与未成熟的移行 B 细胞相关，但 IL-7 组间没有显着差异。结果可能表明在 HCV 缓解或进展期间 TLR7 和 B 细胞之间的相互作用。因此，TLR7 可用作评估慢性感染 HCV 患者的抗病毒治疗效果的有前景的生物标志物，靶向 TLR7 可用作慢性 HCV 的潜在预防和/或治疗剂以及记忆 B 的免疫增强细胞。