Bovine lactoferrin increases the poly(I:C)-induced antiviral response in vitro
Bovine lactoferrin increases the poly(I:C)-induced antiviral response in vitro
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DOI：
10.1139/bcb-2021-0342
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发表时间：
2022-07-13
影响因子：
2.9
通讯作者：
Hirose, Kimiharu
中科院分区：
文献类型：
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作者：
Kobayashi-Sakamoto, Michiyo;Maeda, Toyonobu;Hirose, Kimiharu
牛乳铁蛋白（bLF）是一种天然存在的糖蛋白，具有抗菌和抗病毒活性。我们评估了bLF是否可以预防人肠上皮细胞系Caco-2中的病毒感染。为了评估抗病毒反应，我们测量了干扰素（IFN）表达水平，IFN刺激的基因表达，以及在用bLF和聚肌苷酸-聚胞苷酸（一种模拟病毒感染的双链RNA类似物）处理细胞后，用携带严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）刺突蛋白或水泡性口炎病毒（VSV）-G蛋白的假型病毒感染。用bLF和聚肌胞苷酸联合处理细胞增加Caco-2细胞中几种IFN基因（IFNB、IFNL 1和IFNL 2）和IFN刺激基因（ISG 15、MX 1、IFITM 1和IFITM 3）的mRNA和蛋白质表达。然而，单独使用bLF治疗不会诱导抗病毒反应。此外，联合治疗抑制SARS-CoV-2假型病毒的感染比单独bLF治疗更有效，即使联合治疗增加了编码ACE 2的mRNA的表达。这些结果表明，bLF增加与双链RNA刺激的信号通路相关的抗病毒反应。我们的研究结果还表明，bLF和双链RNA类似物可用于治疗病毒感染，包括由SARS-CoV-2引起的病毒感染。
Bovine lactoferrin (bLF) is a naturally occurring glycoprotein with antibacterial and antiviral activities. We evaluated whether bLF can prevent viral infections in the human intestinal epithelial cell line Caco-2. To assess antiviral responses, we measured the levels of interferon (IFN) expression, IFN-stimulated gene expression, and infection with a pseudotyped virus bearing either severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein or vesicular stomatitis virus (VSV)-G protein after treatment of cells with both bLF and polyinosinic-polycytidylic acid, an analog of double-stranded RNA that mimics viral infec-tion. Combination treatment of cells with both bLF and polyinosinic-polycytidylic acid increased mRNA and protein expression of several IFN genes (IFNB, IFNL1, and IFNL2) and IFN-stimulated genes (ISG15, MX1, IFITM1, and IFITM3) in Caco-2 cells. However, treatment with bLF alone did not induce an antiviral response. Furthermore, combination treatment suppressed infection of the SARS-CoV-2 pseudotyped virus more efficiently than did bLF treatment alone, even though combination treatment in-creased the expression of mRNA encoding ACE2. These results indicate that bLF increases the antiviral response associated with the double-stranded RNA-stimulated signaling pathway. Our results also suggest that bLF and double-stranded RNA analogs can be used to treat viral infections, including those caused by SARS-CoV-2.