Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection.
Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection.
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病毒 UL8 参与齐墩果酸对抗 HSV-1 感染的抗病毒活性
DOI：
10.3389/fmicb.2021.689607
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发表时间：
2021
影响因子：
5.2
通讯作者：
Ren Z
中科院分区：
文献类型：
--
作者：
Shan T;Ye J;Jia J;Wang Z;Jiang Y;Wang Y;Wang Y;Zheng K;Ren Z
1型单纯疱疹病毒（HSV-1）在人类中高度流行，可引起严重疾病，特别是在免疫功能低下的成年人和新生儿中，如角膜炎和单纯疱疹脑炎。目前临床治疗HSV-1感染的药物是阿昔洛韦（ACV），其广泛使用导致了耐药菌株的出现。因此，寻找新的治疗靶点和抗hsv -1药物迫在眉睫。本研究证明齐果酸是一种广泛存在于天然产物中的五环三萜，对不同细胞的acv敏感型和耐药型HSV-1株均具有较强的抗病毒活性。机制研究表明齐墩果酸在感染早期发挥其抗hsv -1的活性，这涉及病毒UL8的失调，UL8是病毒解旋酶-引物酶复合体的一个组成部分，对病毒复制至关重要。此外，齐墩果酸显著改善了HSV-1感染介导的带状虫模型的皮肤损伤。总之，我们的研究表明齐墩果酸可能是临床治疗HSV-1感染相关疾病的潜在候选者。
Herpes simplex virus type 1 (HSV-1) is highly prevalent in humans and can cause severe diseases, especially in immunocompromised adults and newborns, such as keratitis and herpes simplex encephalitis. At present, the clinical therapeutic drug against HSV-1 infection is acyclovir (ACV), and its extensive usage has led to the emergence of ACV-resistant strains. Therefore, it is urgent to explore novel therapeutic targets and anti-HSV-1 drugs. This study demonstrated that Oleanolic acid, a pentacyclic triterpenoid widely existing in natural product, had strong antiviral activity against both ACV-sensitive and -resistant HSV-1 strains in different cells. Mechanism studies showed that Oleanolic acid exerted its anti-HSV-1 activity in the immediate early stage of infection, which involved the dysregulation of viral UL8, a component of viral helicase-primase complex critical for viral replication. In addition, Oleanolic acid significantly ameliorated the skin lesions in an HSV-1 infection mediated zosteriform model. Together, our study suggested that Oleanolic acid could be a potential candidate for clinical therapy of HSV-1 infection-related diseases.
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