PDF(Pubmed)
Abstract：
Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney cells), MDBK (Madin-Darby bovine kidney), and NBL-6 cells (E. Derm cells). Mechanistic investigations revealed that hyperoside induces heme oxygenase-1 expression by activating the c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis, alleviating oxidative stress and triggering a downstream antiviral interferon response. Accordingly, hyperoside inhibits EHV-8 infection. Meanwhile, hyperoside can also mitigate EHV-8-induced injury in the lungs of infected mice. These results indicate that hyperoside may serve as a novel antiviral agent against EHV-8 infection.IMPORTANCEHyperoside has been reported to suppress viral infections, including herpesvirus, hepatitis B virus, infectious bronchitis virus, and severe acute respiratory syndrome coronavirus 2 infection. However, its mechanism of action against equine herpesvirus type 8 (EHV-8) is currently unknown. Here, we demonstrated that hyperoside significantly inhibits EHV-8 adsorption and internalization in susceptible cells. This process induces HO-1 expression via c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis activation, alleviating oxidative stress and triggering an antiviral interferon response. These findings indicate that hyperoside could be very effective as a drug against EHV-8.
摘要：
马疱疹病毒8型（EHV-8）导致马和驴的流产和呼吸道疾病，导致全球马业严重的经济损失。目前,没有针对EHV-8感染的有效疫苗或药物，强调需要一种新型抗病毒药物来预防EHV-8诱导的潜伏感染并降低该病毒的致病性。本研究表明，金丝桃苷可以对RK-13（兔肾细胞）的EHV-8感染发挥抗病毒作用，MDBK(Madin-Darby牛肾)和NBL-6细胞(E.真皮细胞）。机制研究表明，金丝桃苷通过激活c-JunN末端激酶/核因子红系2相关因子2/Kelch样ECH相关蛋白1轴来诱导血红素加氧酶1表达，减轻氧化应激和触发下游抗病毒干扰素反应。因此，金丝桃苷抑制EHV-8感染。同时,金丝桃苷还可以减轻EHV-8引起的感染小鼠肺部损伤。这些结果表明，金丝桃苷可以作为抗EHV-8感染的新型抗病毒剂。据报道，IMPORTANCEHyperoside可以抑制病毒感染，包括疱疹病毒,乙型肝炎病毒，传染性支气管炎病毒，和严重急性呼吸道综合症冠状病毒2感染。然而,其抗马疱疹病毒8型（EHV-8）的作用机制目前尚不清楚。这里,我们证明金丝桃苷显著抑制EHV-8在易感细胞中的吸附和内化。此过程通过c-JunN末端激酶/核因子红系2相关因子2/Kelch样ECH相关蛋白1轴激活诱导HO-1表达，减轻氧化应激和引发抗病毒干扰素反应。这些发现表明，金丝桃苷作为抗EHV-8的药物可能非常有效。
