Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, 80055, Naples, Italy.
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137, Naples, Italy.
Sci Rep. 2017 Oct 17;7(1):13306. doi: 10.1038/s41598-017-13717-1.
Bovine herpesvirus 1 (BoHV-1) can provoke conjunctivitis, abortions and shipping fever. BoHV-1 infection can also cause immunosuppression and increased susceptibility to secondary bacterial infections, leading to pneumonia and occasionally to death. Herein, we investigated the influence of MG-132, a proteasome inhibitor, on BoHV-1 infection in bovine kidney (MDBK) cells. Infection of MDBK cells with BoHV-1 induces apoptotic cell death that enhances virus release. Whereas, MG-132 inhibited virus-induced apoptosis and stimulated autophagy. Protein expression of viral infected cell protein 0 (bICP0), which is constitutively expressed during infection and is able to stimulate Nuclear factor kappa B (NF-κB), was completely inhibited by MG-132. These results were accompanied by a significant delay in the NF-κB activation. Interestingly, the efficient virus release provoked by BoHV-1-induced apoptosis was significantly reduced by MG-132. Overall, this study suggests that MG-132, through the activation of autophagy, may limit BoHV-1 replication during productive infection, by providing an antiviral defense mechanism.
牛疱疹病毒 1(BoHV-1)可引起结膜炎、流产和运输热。BoHV-1 感染还可导致免疫抑制和继发细菌性感染的易感性增加,导致肺炎,偶尔导致死亡。在此,我们研究了蛋白酶体抑制剂 MG-132 对牛肾(MDBK)细胞中 BoHV-1 感染的影响。BoHV-1 感染 MDBK 细胞可诱导凋亡细胞死亡,从而促进病毒释放。然而,MG-132 抑制了病毒诱导的细胞凋亡并刺激了自噬。在感染过程中持续表达并能够刺激核因子 kappa B(NF-κB)的病毒感染细胞蛋白 0(bICP0)的蛋白表达被 MG-132 完全抑制。这些结果伴随着 NF-κB 激活的显著延迟。有趣的是,MG-132 显著降低了由 BoHV-1 诱导的细胞凋亡引起的有效病毒释放。总的来说,这项研究表明,MG-132 通过自噬的激活,可能通过提供抗病毒防御机制,在产感染期间限制 BoHV-1 的复制。