Abstract: Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main role in inflammatory cytokine responses. Similarly, alveolar macrophages produce IFN-β, IFN-α, TNF-α, IL-6, CXCL10, and CCL3, while alternatively activated macrophages differentiate at the late phase, and require IL-13 or IL-4 cytokines. Furthermore, activated NKT cells secrete IL-13 and IL-4 that cause lung epithelial, endothelial and fibroblasts to secrete eotaxin that enhances the recruitment of eosinophil to the lung. CD8⁺ and CD4⁺T cells infection by the virus decreases the IFN-γ and IL-2 production. Despite this, both are involved in terminating virus replication. CD8⁺T cells produce a larger amount of IFN-γ than CD4⁺T cells, and CD8⁺T cells activated under type 2 conditions produce IL-4, down regulating CD8 expression, granzyme and IFN-γ production. Antiviral inhibitors inhibit biological functions of viral proteins. Some of them directly target the virus replication machinery and are effective at later stages of infection; while others inhibit F protein dependent fusion and syncytium formation. TMC353121 reduces inflammatory cytokines, TNF-α, IL-6, and IL-1β and chemokines, KC, IP-10, MCP and MIP1-α. EDP-938 inhibits viral nucleoprotein (N), while GRP-156784 blocks the activity of respiratory syncytial virus ribonucleic acid (RNA) polymerase. PC786 inhibits non-structural protein 1 (NS-1) gene, RANTES transcripts, virus-induced CCL5, IL-6, and mucin increase. In general, it is an immune reaction that is blamed for the disease severity and pathogenesis in respiratory syncytial virus infection. Anti-viral inhibitors not only inhibit viral entry and replication, but also may reduce inflammatory cytokines and chemokines. Many respiratory syncytial virus inhibitors are proposed; however, only palivizumab and ribavirin are approved for prophylaxis and treatment, respectively. Hence, this review is focused on immunity cell responses to respiratory syncytial virus and the role of antiviral inhibitors.

Keywords: immune cells, respiratory syncytial virus, antiviral inhibitors


中文翻译：

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免疫细胞对 RSV 的反应和抗病毒抑制剂的作用：系统评价

摘要：抗原呈递细胞识别呼吸道合胞病毒抗原，产生作用于免疫细胞的细胞因子和趋化因子。树突状细胞在炎性细胞因子反应中起主要作用。同样，肺泡巨噬细胞产生 IFN-β、IFN-α、TNF-α、IL-6、CXCL10 和 CCL3，而交替激活的巨噬细胞在晚期分化，需要 IL-13 或 IL-4 细胞因子。此外，活化的 NKT 细胞分泌 IL-13 和 IL-4，导致肺上皮细胞、内皮细胞和成纤维细胞分泌嗜酸性粒细胞趋化因子，增强嗜酸性粒细胞向肺部的募集。病毒感染CD8 ⁺和 CD4 ^{+ T 细胞会降低 IFN-γ 和 IL-2 的产生。}尽管如此，两者都参与终止病毒复制。CD8 ^{+T 细胞比 CD4 +} T细胞产生更大量的 IFN-γ ，而 CD8 ⁺在 2 型条件下激活的 T 细胞产生 IL-4，下调 CD8 表达、颗粒酶和 IFN-γ 产生。抗病毒抑制剂抑制病毒蛋白的生物学功能。其中一些直接针对病毒复制机制，在感染后期有效；而其他抑制 F 蛋白依赖性融合和合胞体形成。TMC353121 减少炎性细胞因子、TNF-α、IL-6 和 IL-1β 以及趋化因子、KC、IP-10、MCP 和 MIP1-α。EDP​​-938 抑制病毒核蛋白 (N)，而 GRP-156784 阻断呼吸道合胞病毒核糖核酸 (RNA) 聚合酶的活性。PC786 抑制非结构蛋白 1 (NS-1) 基因、RANTES 转录本、病毒诱导的 CCL5、IL-6 和粘蛋白增加。一般来说，这是一种免疫反应，导致呼吸道合胞病毒感染的疾病严重程度和发病机制。抗病毒抑制剂不仅可以抑制病毒进入和复制，还可以减少炎性细胞因子和趋化因子。提出了许多呼吸道合胞病毒抑制剂；然而，只有帕利珠单抗和利巴韦林分别被批准用于预防和治疗。因此，这篇综述的重点是免疫细胞对呼吸道合胞病毒的反应和抗病毒抑制剂的作用。

Keywords:免疫细胞, 呼吸道合胞病毒, 抗病毒抑制剂