Department of Preventive Dentistry, Ohu University School of Dentistry, Koriyama, Fukushima 963-8611, Japan.
Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama, Fukushima 963-8611, Japan.
Biochem Cell Biol. 2022 Aug 1;100(4):338-348. doi: 10.1139/bcb-2021-0342. Epub 2022 Aug 18.
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 infection. Combination treatment of cells with both bLF and polyinosinic-polycytidylic acid increased mRNA and protein expression of several IFN genes (, and ) and IFN-stimulated genes (, and ) 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 increased 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.
牛乳铁蛋白（bLF）是一种具有抗菌和抗病毒活性的天然糖蛋白。我们评估了 bLF 是否可以预防人肠道上皮细胞系 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、IFN 刺激基因表达的水平，并在细胞用 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）处理后，评估了感染带有严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突蛋白或水疱性口炎病毒（VSV）-G 蛋白的假型病毒的情况。用 bLF 和聚肌苷酸-聚胞苷酸联合处理细胞可增加 Caco-2 细胞中几种 IFN 基因（、和）和 IFN 刺激基因（、和）的 mRNA 和蛋白表达。然而，单独用 bLF 处理不会诱导抗病毒反应。此外，联合治疗比单独用 bLF 治疗更有效地抑制 SARS-CoV-2 假型病毒的感染，尽管联合治疗增加了编码 ACE2 的 mRNA 的表达。这些结果表明，bLF 增加了与双链 RNA 刺激的信号通路相关的抗病毒反应。我们的结果还表明，bLF 和双链 RNA 类似物可用于治疗病毒感染，包括由 SARS-CoV-2 引起的感染。
