Department of Biology, University of Waterloo, Waterloo, ON, Canada; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
Department of Biology, University of Waterloo, Waterloo, ON, Canada.
Antiviral Res. 2019 Feb;162:151-162. doi: 10.1016/j.antiviral.2019.01.001. Epub 2019 Jan 6.
The heat-shock protein 70 (Hsp70) inhibitor, VER-155008 (VER), was explored as a potential antiviral agent for two RNA viruses important to fish aquaculture, viral hemorrhagic septicemia virus (VHSV) and infectious pancreatic necrosis virus (IPNV). Studies were done at a temperature of 14 °C, and with cell lines commonly used to propagate these viruses. These were respectively EPC from fathead minnow for VHSV and CHSE-214 from Chinook salmon embryo for IPNV. Additionally, both viruses were studied with the Atlantic salmon heart endothelial cell line ASHe. For both VHSV and IPNV, 25 μM VER impeded replication. This was evidenced by delays in the development of cytopathic effect (CPE) and the expression of viral proteins, N for VHSV and VP2 for IPNV, and by less production of viral RNA and of viral titre. As VER inhibits the activity of Hsp70 family members, these results suggest that VHSV and IPNV utilize one or more Hsp70s in their life cycles. Yet neither virus induced Hsp70. Surprisingly VER alone induced Hsp70, but whether this induction modulated VER's antiviral effects is unknown. Exploring this apparent paradox in the future should improve the usefulness of VER as an antiviral agent.
热休克蛋白 70（Hsp70）抑制剂 VER-155008（VER）被探索作为两种对鱼类养殖至关重要的 RNA 病毒（病毒性出血性败血症病毒（VHSV）和传染性胰脏坏死病毒（IPNV）的潜在抗病毒药物。这些研究是在 14°C 的温度下进行的，并且使用了通常用于繁殖这些病毒的细胞系。这些细胞系分别是用于 VHSV 的胖头鲦鱼的 EPC 和用于 IPNV 的奇努克鲑鱼胚胎的 CHSE-214。此外，还用大西洋三文鱼心脏内皮细胞系 ASHe 研究了这两种病毒。对于 VHSV 和 IPNV，25µM 的 VER 抑制了复制。这表现在细胞病变效应（CPE）的发展和病毒蛋白 N（用于 VHSV）和 VP2（用于 IPNV）的表达延迟，以及病毒 RNA 的产生和病毒滴度降低。由于 VER 抑制了 Hsp70 家族成员的活性，这些结果表明 VHSV 和 IPNV 在其生命周期中利用了一种或多种 Hsp70。然而，两种病毒都没有诱导 Hsp70。令人惊讶的是，单独的 VER 诱导了 Hsp70，但这种诱导是否调节了 VER 的抗病毒作用尚不清楚。未来探索这一明显的悖论应该会提高 VER 作为抗病毒药物的有用性。
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