关键词: Apoptosis HAdV-14 ROS Selenocystine

Mesh : Humans Reactive Oxygen Species / metabolism Tumor Suppressor Protein p53 / metabolism Poly(ADP-ribose) Polymerase Inhibitors / pharmacology Adenoviruses, Human / genetics Selenium / pharmacology metabolism Apoptosis Antiviral Agents / pharmacology Signal Transduction Adenoviridae Infections

来  源:   DOI:10.1016/j.jtemb.2023.127213

Abstract:
BACKGROUND: Human Adenovirus (HAdV) can cause severe respiratory symptoms in people with low immunity and there is no targeted treatment for adenovirus infection. Anti-adenoviral drugs have high clinical significance for inhibiting adenovirus infection. Selenium (Se) plays an important role in anti-oxidation, redox signal transduction, and redox homeostasis. The excellent biological activity of Se is mainly achieved by being converted into selenocystine (SeC). Se participates in the active sites of various selenoproteins in the form of SeC. The ability of SeC to resist the virus has raised high awareness due to its unique antioxidative activity in recent years. The antiviral ability of the SeC was determined by detecting the infection rate of the virus in the cells.
METHODS: The experiment mainly investigated the antiviral mechanism of SeC by locating the virus in the cell, detecting the generation of ROS, observing the DNA status of the cell, and monitoring the mitochondrial membrane potential.
RESULTS: In the present study, SeC was designed to resist A549 cells infections caused by HAdV-14. SeC could prevent HAdV-14 from causing cell apoptosis-related to DNA damage. SeC significantly inhibited ROS generation and protect the cells from oxidative damage induced by ROS against HAdV-14. SeC induced the increase of antiviral cytokines such as IL-6 and IL-8 by activating the Jak2 signaling pathway, and repaired DNA lesions by suppressing ATR, p53, and PARP signaling pathways.
CONCLUSIONS: SeC might provide an effective selenium species with antiviral properties for the therapies against HAdV-14.
摘要:
背景:人腺病毒(HAdV)可在免疫力低下的人群中引起严重的呼吸道症状,并且尚无针对腺病毒感染的靶向治疗方法。抗腺病毒药物对抑制腺病毒感染具有较高的临床意义。硒(Se)在抗氧化中具有重要作用,氧化还原信号转导,和氧化还原稳态。硒的优良生物活性主要通过转化为硒代半胱氨酸(SeC)来实现。Se以SeC的形式参与各种硒蛋白的活性位点。近年来,由于其独特的抗氧化活性,SeC抵抗病毒的能力引起了人们的高度关注。通过检测病毒在细胞中的感染率来确定SeC的抗病毒能力。
方法:本实验主要通过在细胞中定位病毒来研究SeC的抗病毒机制,检测ROS的产生,观察细胞的DNA状态,监测线粒体膜电位.
结果:在本研究中,SeC被设计为抵抗由HAdV-14引起的A549细胞感染。SeC可以防止HAdV-14引起与DNA损伤相关的细胞凋亡。SeC显著抑制ROS的生成,保护细胞免受ROS诱导的HAdV-14氧化损伤。SeC通过激活Jak2信号通路诱导IL-6和IL-8等抗病毒细胞因子的增加,通过抑制ATR修复DNA损伤,p53和PARP信号通路。
结论:SeC可能为HAdV-14的治疗提供具有抗病毒特性的有效硒物质。
公众号