Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an City, Shandong Province, 271018, China; College of Veterinary Medicine, Shandong Agricultural University, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an City, Shandong Province, 271018, China.
Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an City, Shandong Province, 271018, China; College of Veterinary Medicine, Shandong Agricultural University, Tai'an City, Shandong Province, 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, Tai'an City, Shandong Province, 271018, China.
Vet Microbiol. 2020 Dec;251:108885. doi: 10.1016/j.vetmic.2020.108885. Epub 2020 Oct 10.
Heme Oxygenase-1 (HO-1) is a ubiquitously expressed enzyme which plays important functions in antioxidant, anti-inflammatory and anti-apoptosis. Recent studies have demonstrated that HO-1 also has significant antiviral properties, inhibiting the replication of some kinds of viruses such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and dengue fever virus (DFV). In this study, we evaluated the role of HO-1 in Duck Tembusu virus (DTMUV) replication in vitro. The results showed that, the mRNA expression level of HO-1 was transient up-regulated and then significantly decreased in duck embryo fibroblast (DEF) infected with DTMUV. HO-1 induction by transfection of HO-1 over-expression plasmid or treatment with cobalt protoporphyrin (CoPP), a potent HO-1 inducer, could inhibit DTMUV replication effectively. In contrast, HO-1 siRNA knockdown in DEF increased DTMUV replication, implied that HO-1 was an important cellular factor against DTMUV replication. Furthermore, we found that ferric ion (Fe) but not biliverdin and carbon monoxide, products of heme degradation by HO-1, mediated the HO-1-induced anti-DTMUV effect. Overall, these finding revealed that a drug induced the HO-1 signal pathway was a promising strategy for treating DTMUV infection.
血红素加氧酶-1(HO-1)是一种广泛表达的酶,在抗氧化、抗炎和抗细胞凋亡中发挥重要作用。最近的研究表明,HO-1 还具有显著的抗病毒特性,能抑制某些病毒如人类免疫缺陷病毒(HIV)、丙型肝炎病毒(HCV)和登革热病毒(DFV)的复制。在本研究中,我们评估了 HO-1 在鸭坦布苏病毒(DTMUV)体外复制中的作用。结果表明,HO-1 的 mRNA 表达水平在感染 DTMUV 的鸭胚成纤维细胞(DEF)中短暂上调,然后显著下降。用 HO-1 过表达质粒转染或用强效 HO-1 诱导剂钴原卟啉(CoPP)诱导 HO-1 可有效抑制 DTMUV 的复制。相反,DEF 中的 HO-1 siRNA 敲低会增加 DTMUV 的复制,表明 HO-1 是一种对抗 DTMUV 复制的重要细胞因子。此外,我们发现铁离子(Fe)而不是胆红素和一氧化碳,是 HO-1 降解血红素的产物,介导了 HO-1 诱导的抗 DTMUV 作用。总的来说,这些发现表明,诱导 HO-1 信号通路的药物可能是治疗 DTMUV 感染的一种有前途的策略。