Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China.
Department of Microbiology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China.
Viruses. 2024 Sep 23;16(9):1503. doi: 10.3390/v16091503.
Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice for several decades to treat various medical conditions. In this study, the anti-CVB effect of NAC was investigated. We show that NAC dramatically suppressed viral replication and alleviated cardiac injury induced by CVB3. To further study the antiviral mechanism of NAC, RNA-sequencing was performed for CVB3-infected cells with NAC treatment. We found that eukaryotic elongation factor 1 alpha 1 () is one of the most upregulated genes in CVB3-infected cells. However, , the highly homologous isoform of , remains unchanged. expression was significantly suppressed by NAC treatment in CVB3-infected cells, while was not affected. eEF1A1 knockdown significantly inhibited CVB3 replication, implicating that eEF1A1 facilitates viral replication. Importantly, we show that eEF1A1, which was not expressed in the myocardia of newborn mice, was significantly upregulated by CVB3 infection. NAC markedly downregulated the expression of eEF1A1 but not eEF1A2 in the myocardia of CVB3-infected mice. Furthermore, NAC accelerated eEF1A1 degradation by promoting autophagy in CVB3-infected cells. We show that p62, one of the critical adaptors of autophagic targets, interacts with eEF1A1 and was downregulated in CVB3-infected cells upon NAC treatment. Taken together, this study demonstrated that NAC shows a potent anti-CVB effect through the downregulation of eEF1A1.
B 组柯萨奇病毒（CVB）是心肌炎的致病病原体之一，可能进展为心肌病。CVB 的发病机制尚不完全清楚，也没有有效的抗病毒治疗方法。N-乙酰半胱氨酸（NAC）作为经典的抗氧化剂，已在临床上使用数十年，用于治疗各种疾病。在本研究中，研究了 NAC 对 CVB 的抗病毒作用。结果表明，NAC 可显著抑制病毒复制并减轻 CVB3 诱导的心脏损伤。为了进一步研究 NAC 的抗病毒机制，对 NAC 处理的 CVB3 感染细胞进行了 RNA 测序。我们发现，真核延伸因子 1 阿尔法 1（）是 CVB3 感染细胞中上调最明显的基因之一。然而，作为其高度同源的同种型，仍然保持不变。NAC 处理显著抑制了 CVB3 感染细胞中的表达，而对 没有影响。eEF1A1 敲低显著抑制了 CVB3 的复制，表明 eEF1A1 促进了病毒的复制。重要的是，我们表明，在新生小鼠的心肌中不表达的 eEF1A1，在 CVB3 感染后显著上调。NAC 显著下调了 CVB3 感染小鼠心肌中 eEF1A1 的表达，但对 eEF1A2 没有影响。此外，NAC 通过促进 CVB3 感染细胞中的自噬来加速 eEF1A1 的降解。结果表明，p62 是自噬靶标的关键衔接子之一，与 eEF1A1 相互作用，并在 NAC 处理的 CVB3 感染细胞中下调。总之，这项研究表明，NAC 通过下调 eEF1A1 表现出强大的抗 CVB 作用。
