Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator Expression

Herpes simplex virus type 1 (HSV-1) infection induces various clinical disorders, such as herpes simplex encephalitis (HSE), herpes simplex keratitis (HSK), and genital herpes. In clinical intervention, acyclovir (ACV) is the major therapeutic drug used to suppress HSV-1; however, ACV-resistant stra...

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Main Authors: Ye Liu, Qiao You, Fang Zhang, Deyan Chen, Zhenping Huang, Zhiwei Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-08-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2021.722748/full
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spelling doaj-601a0d3d3d9540bcb267d0ddadae34c12021-09-03T22:20:16ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-08-011210.3389/fmicb.2021.722748722748Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator ExpressionYe Liu0Ye Liu1Qiao You2Fang Zhang3Deyan Chen4Zhenping Huang5Zhiwei Wu6Zhiwei Wu7Zhiwei Wu8Medical School of Nanjing University, Nanjing, ChinaDepartment of Ophthalmology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, ChinaMedical School of Nanjing University, Nanjing, ChinaMedical School of Nanjing University, Nanjing, ChinaMedical School of Nanjing University, Nanjing, ChinaDepartment of Ophthalmology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, ChinaJiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, ChinaState Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, ChinaSchool of Life Sciences, Ningxia University, Yinchuan, ChinaHerpes simplex virus type 1 (HSV-1) infection induces various clinical disorders, such as herpes simplex encephalitis (HSE), herpes simplex keratitis (HSK), and genital herpes. In clinical intervention, acyclovir (ACV) is the major therapeutic drug used to suppress HSV-1; however, ACV-resistant strains have gradually increased. In the present study, harringtonine (HT) significantly inhibited infection of HSV-1 as well as two ACV-resistant strains, including HSV-1 blue and HSV-1 153. Time-of-drug addition assay further revealed that HT mainly reduced the early stage of HSV-1 infection. We also demonstrated that HT mainly affected herpes virus entry mediator (HVEM) expression as shown by qPCR, Western Blot, and Immunofluorescence. Collectively, HT showed antiviral activity against HSV-1 and ACV-resistant strains by targeting HVEM and could be a promising therapeutic candidate for mitigating HSV-1-induced-pathogenesis.https://www.frontiersin.org/articles/10.3389/fmicb.2021.722748/fullharringtonineherpes simplex virus type 1acyclovir-resistantherpes virus entry mediatorentry receptor
collection DOAJ
language English
format Article
sources DOAJ
author Ye Liu
Ye Liu
Qiao You
Fang Zhang
Deyan Chen
Zhenping Huang
Zhiwei Wu
Zhiwei Wu
Zhiwei Wu
spellingShingle Ye Liu
Ye Liu
Qiao You
Fang Zhang
Deyan Chen
Zhenping Huang
Zhiwei Wu
Zhiwei Wu
Zhiwei Wu
Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator Expression
Frontiers in Microbiology
harringtonine
herpes simplex virus type 1
acyclovir-resistant
herpes virus entry mediator
entry receptor
author_facet Ye Liu
Ye Liu
Qiao You
Fang Zhang
Deyan Chen
Zhenping Huang
Zhiwei Wu
Zhiwei Wu
Zhiwei Wu
author_sort Ye Liu
title Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator Expression
title_short Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator Expression
title_full Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator Expression
title_fullStr Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator Expression
title_full_unstemmed Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator Expression
title_sort harringtonine inhibits herpes simplex virus type 1 infection by reducing herpes virus entry mediator expression
publisher Frontiers Media S.A.
series Frontiers in Microbiology
issn 1664-302X
publishDate 2021-08-01
description Herpes simplex virus type 1 (HSV-1) infection induces various clinical disorders, such as herpes simplex encephalitis (HSE), herpes simplex keratitis (HSK), and genital herpes. In clinical intervention, acyclovir (ACV) is the major therapeutic drug used to suppress HSV-1; however, ACV-resistant strains have gradually increased. In the present study, harringtonine (HT) significantly inhibited infection of HSV-1 as well as two ACV-resistant strains, including HSV-1 blue and HSV-1 153. Time-of-drug addition assay further revealed that HT mainly reduced the early stage of HSV-1 infection. We also demonstrated that HT mainly affected herpes virus entry mediator (HVEM) expression as shown by qPCR, Western Blot, and Immunofluorescence. Collectively, HT showed antiviral activity against HSV-1 and ACV-resistant strains by targeting HVEM and could be a promising therapeutic candidate for mitigating HSV-1-induced-pathogenesis.
topic harringtonine
herpes simplex virus type 1
acyclovir-resistant
herpes virus entry mediator
entry receptor
url https://www.frontiersin.org/articles/10.3389/fmicb.2021.722748/full
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