BK21 Graduate program, Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital, Seoul, South Korea.
Department of Medicine, Korea University College of Medicine, Seoul, South Korea.
Front Cell Infect Microbiol. 2022 Apr 21;12:850744. doi: 10.3389/fcimb.2022.850744. eCollection 2022.
The endemic and pandemic caused by respiratory virus infection are a major cause of mortality and morbidity globally. Thus, broadly effective antiviral drugs are needed to treat respiratory viral diseases. Small extracellular vesicles derived from human umbilical cord mesenchymal stem cells (U-exo) have recently gained attention as a cell-free therapeutic strategy due to their potential for safety and efficacy. Anti-viral activities of U-exo to countermeasure respiratory virus-associated diseases are currently unknown. Here, we tested the antiviral activities of U-exo following influenza A/B virus (IFV) and human seasonal coronavirus (HCoV) infections . Cells were subject to IFV or HCoV infection followed by U-exo treatment. U-exo treatment significantly reduced IFV or HCoV replication and combined treatment with recombinant human interferon-alpha protein (IFN-α) exerted synergistically enhanced antiviral effects against IFV or HCoV. Interestingly, microRNA (miR)-125b, which is one of the most abundantly expressed small RNAs in U-exo, was found to suppress IFV replication possibly the induction of IFN-stimulated genes (ISGs). Furthermore, U-exo markedly enhanced RNA virus-triggered IFN signaling and ISGs production. Similarly, human nasal epithelial cells cultured at the air-liquid interface (ALI) studies broadly effective anti-viral and anti-inflammatory activities of U-exo against IFV and HCoV, suggesting the potential role of U-exo as a promising intervention for respiratory virus-associated diseases.
呼吸道病毒感染引起的地方性和流行性疾病是全球范围内导致死亡率和发病率的主要原因。因此，需要有广泛有效的抗病毒药物来治疗呼吸道病毒疾病。源自人脐带间充质干细胞（U-exo）的小细胞外囊泡由于其安全性和有效性而成为一种无细胞治疗策略，最近引起了人们的关注。U-exo 对抗呼吸道病毒相关疾病的抗病毒活性目前尚不清楚。在这里，我们测试了 U-exo 在流感 A/B 病毒（IFV）和人类季节性冠状病毒（HCoV）感染后的抗病毒活性。细胞先感染 IFV 或 HCoV，然后用 U-exo 处理。U-exo 处理显著降低了 IFV 或 HCoV 的复制，而与重组人干扰素-α蛋白（IFN-α）联合治疗则对 IFV 或 HCoV 产生协同增强的抗病毒作用。有趣的是，在 U-exo 中表达最丰富的小 RNA（miR）-125b 之一被发现可能通过诱导干扰素刺激基因（ISGs）来抑制 IFV 复制。此外，U-exo 显著增强了 RNA 病毒触发的 IFN 信号和 ISGs 的产生。同样，在气液界面（ALI）培养的人鼻上皮细胞中进行的研究表明，U-exo 对 IFV 和 HCoV 具有广泛有效的抗病毒和抗炎活性，这表明 U-exo 作为一种有前途的呼吸道病毒相关疾病干预措施具有潜在作用。
