Modulation of Memory B Cell Phenotypes and Toll-Like Receptor-7 in Chronic Hepatitis C Virus Infection During Direct-Acting Antiviral Interferon-Free Therapy: Correlation with Interleukin-7

• Published in: Viral immunology Vol. 34; no. 4; p. 227
• Main Authors: Moustafa, Hanan, Madkour, Marwa, Hamed, Fathi, Abouelnazar, Salma, Abo Elwafa, Reham, Moaaz, Mai
• Format: Journal Article
• Language: English
• Published: United States 01.05.2021
• Subjects: Antiviral Agents - therapeutic use; Hepacivirus - genetics; Hepatitis C - drug therapy; Hepatitis C, Chronic; Humans; Interferons - therapeutic use; Interleukin-7; Memory B Cells - drug effects; Phenotype; Prospective Studies; Toll-Like Receptor 7 - drug effects; Toll-Like Receptor 7 - genetics; HCV; TLR7; direct-acting antiviral interferon-free therapy; memory B cell; IL-7
• ISSN: 1557-8976
• DOI: 10.1089/vim.2020.0110

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.