Hepatobiliary Surgery, The Sixth People's Hospital of Shenyang, Shenyang, China.
The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine/Medical Management Office, China.
Microb Pathog. 2024 Sep;194:106821. doi: 10.1016/j.micpath.2024.106821. Epub 2024 Jul 30.
Interferon-alpha (IFNα) is a common treatment for chronic hepatitis B virus (HBV) infection, but its efficacy varies widely among patients. GTPASE, an interferon-stimulated gene (ISG), has recently been identified as a factor in antiviral immunity, though its role in HBV infection is not fully understood.
This study investigates the role of GTPASE in enhancing the antiviral effects of IFNα against HBV and elucidates its mechanism of action.
We analyzed the impact of GTPASE overexpression and silencing on HBV replication and clearance in HBV-infected cells. Molecular docking studies assessed the interaction between GTPASE and HBV surface antigens (HBs). Clinical samples from HBV patients undergoing Peg-IFNα treatment were also evaluated for GTPASE expression and its correlation with treatment efficacy.
Overexpression of GTPASE led to significant inhibition of HBV replication, increased HBeAg seroconversion, and enhanced HBsAg clearance. GTPASE directly bound to HBs proteins, reducing their levels and affecting viral particle formation. Silencing GTPASE reduced these effects, while combined treatment with Peg-IFNα and GTPASE overexpression further improved antiviral outcomes. Mutational analysis revealed that specific sites in GTPASE are crucial for its antiviral activity.
GTPASE acts as a positive regulator in IFNα-induced antiviral immunity against HBV. It enhances the therapeutic efficacy of IFNα by targeting HBs and modulating viral replication. GTPASE levels may serve as a predictive biomarker for response to Peg-IFNα therapy, highlighting its potential for improving individualized treatment strategies for chronic HBV infection.
干扰素-α（IFNα）是治疗慢性乙型肝炎病毒（HBV）感染的常用药物，但在不同患者中的疗效差异很大。GTPASE 是一种干扰素刺激基因（ISG），最近被认为是抗病毒免疫的一个因素，但它在 HBV 感染中的作用尚不完全清楚。
本研究旨在探讨 GTPASE 在增强 IFNα 对 HBV 的抗病毒作用中的作用，并阐明其作用机制。
我们分析了 GTPASE 过表达和沉默对 HBV 感染细胞中 HBV 复制和清除的影响。分子对接研究评估了 GTPASE 与 HBV 表面抗原（HBs）之间的相互作用。还评估了接受 Peg-IFNα 治疗的 HBV 患者的临床样本中 GTPASE 的表达及其与治疗效果的相关性。
GTPASE 的过表达导致 HBV 复制的显著抑制、HBeAg 血清转换增加和 HBsAg 清除增强。GTPASE 直接与 HBs 蛋白结合，降低其水平并影响病毒颗粒形成。GTPASE 的沉默降低了这些效果，而 Peg-IFNα 和 GTPASE 过表达的联合治疗进一步改善了抗病毒效果。突变分析表明，GTPASE 中的特定位点对于其抗病毒活性至关重要。
GTPASE 作为 IFNα 诱导的抗 HBV 抗病毒免疫的正调节剂发挥作用。它通过靶向 HBs 和调节病毒复制来增强 IFNα 的治疗效果。GTPASE 水平可能作为对 Peg-IFNα 治疗反应的预测生物标志物，突出了其在改善慢性 HBV 感染个体化治疗策略中的潜力。
