Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection

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 exten...

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Main Authors: Tianhao Shan, Ju Ye, Jiaoyan Jia, Zhaoyang Wang, Yuzhou Jiang, Yiliang Wang, Yifei Wang, Kai Zheng, Zhe Ren
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Microbiology
Subjects:
UL8
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2021.689607/full
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language English
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author Tianhao Shan
Tianhao Shan
Tianhao Shan
Tianhao Shan
Tianhao Shan
Tianhao Shan
Ju Ye
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yifei Wang
Yifei Wang
Yifei Wang
Yifei Wang
Yifei Wang
Yifei Wang
Kai Zheng
Zhe Ren
Zhe Ren
Zhe Ren
Zhe Ren
Zhe Ren
Zhe Ren
spellingShingle Tianhao Shan
Tianhao Shan
Tianhao Shan
Tianhao Shan
Tianhao Shan
Tianhao Shan
Ju Ye
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yifei Wang
Yifei Wang
Yifei Wang
Yifei Wang
Yifei Wang
Yifei Wang
Kai Zheng
Zhe Ren
Zhe Ren
Zhe Ren
Zhe Ren
Zhe Ren
Zhe Ren
Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection
Frontiers in Microbiology
herpes simplex virus type 1
Oleanolic acid
UL8
helicase-primase complex
zosteriform model
author_facet Tianhao Shan
Tianhao Shan
Tianhao Shan
Tianhao Shan
Tianhao Shan
Tianhao Shan
Ju Ye
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Jiaoyan Jia
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Zhaoyang Wang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yuzhou Jiang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yiliang Wang
Yifei Wang
Yifei Wang
Yifei Wang
Yifei Wang
Yifei Wang
Yifei Wang
Kai Zheng
Zhe Ren
Zhe Ren
Zhe Ren
Zhe Ren
Zhe Ren
Zhe Ren
author_sort Tianhao Shan
title Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection
title_short Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection
title_full Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection
title_fullStr Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection
title_full_unstemmed Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection
title_sort viral ul8 is involved in the antiviral activity of oleanolic acid against hsv-1 infection
publisher Frontiers Media S.A.
series Frontiers in Microbiology
issn 1664-302X
publishDate 2021-07-01
description 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.
topic herpes simplex virus type 1
Oleanolic acid
UL8
helicase-primase complex
zosteriform model
url https://www.frontiersin.org/articles/10.3389/fmicb.2021.689607/full
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spelling doaj-53c2fd2103824c66bf60c554d975032a2021-07-20T12:04:11ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-07-011210.3389/fmicb.2021.689607689607Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 InfectionTianhao Shan0Tianhao Shan1Tianhao Shan2Tianhao Shan3Tianhao Shan4Tianhao Shan5Ju Ye6Jiaoyan Jia7Jiaoyan Jia8Jiaoyan Jia9Jiaoyan Jia10Jiaoyan Jia11Jiaoyan Jia12Zhaoyang Wang13Zhaoyang Wang14Zhaoyang Wang15Zhaoyang Wang16Zhaoyang Wang17Zhaoyang Wang18Yuzhou Jiang19Yuzhou Jiang20Yuzhou Jiang21Yuzhou Jiang22Yuzhou Jiang23Yuzhou Jiang24Yiliang Wang25Yiliang Wang26Yiliang Wang27Yiliang Wang28Yiliang Wang29Yiliang Wang30Yifei Wang31Yifei Wang32Yifei Wang33Yifei Wang34Yifei Wang35Yifei Wang36Kai Zheng37Zhe Ren38Zhe Ren39Zhe Ren40Zhe Ren41Zhe Ren42Zhe Ren43Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, ChinaKey Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, ChinaDepartment of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaGuangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, ChinaNational Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Plant Chemistry in Qinghai-Tibet Plateau, Qinghai University for Nationalities, Xining, ChinaInstitute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, ChinaKey Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, ChinaDepartment of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaGuangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, ChinaNational Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaInstitute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, ChinaKey Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, ChinaDepartment of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaGuangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, ChinaNational Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaInstitute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, ChinaKey Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, ChinaDepartment of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaGuangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, ChinaNational Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaInstitute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, ChinaKey Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, ChinaDepartment of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaGuangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, ChinaNational Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaInstitute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, ChinaKey Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, ChinaDepartment of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaGuangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, ChinaNational Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, ChinaInstitute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaKey Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, ChinaKey Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, ChinaDepartment of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, ChinaGuangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, ChinaNational Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, ChinaHerpes 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.https://www.frontiersin.org/articles/10.3389/fmicb.2021.689607/fullherpes simplex virus type 1Oleanolic acidUL8helicase-primase complexzosteriform model