Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense

Myricetin, a polyhydroxyflavone compound, is one of the main ingredients of various human foods and therefore also known as dietary flavonoids. Due to the continuous emergence of resistant strains of herpesviruses, novel control measures are required. In the present study, myricetin exhibited potent...

Full description

Bibliographic Details
Main Authors: Huaiyue Hu, Zhiqiang Hu, Yingying Zhang, Hongping Wan, Zhongqiong Yin, Lixia Li, Xiaoxia Liang, Xinghong Zhao, Lizi Yin, Gang Ye, Yuan-Feng Zou, Huaqiao Tang, Renyong Jia, Yaqin Chen, Hao Zhou, Xu Song
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2022.985108/full
_version_ 1798033826225586176
author Huaiyue Hu
Zhiqiang Hu
Yingying Zhang
Hongping Wan
Zhongqiong Yin
Lixia Li
Xiaoxia Liang
Xinghong Zhao
Lizi Yin
Gang Ye
Yuan-Feng Zou
Huaqiao Tang
Renyong Jia
Yaqin Chen
Hao Zhou
Hao Zhou
Xu Song
author_facet Huaiyue Hu
Zhiqiang Hu
Yingying Zhang
Hongping Wan
Zhongqiong Yin
Lixia Li
Xiaoxia Liang
Xinghong Zhao
Lizi Yin
Gang Ye
Yuan-Feng Zou
Huaqiao Tang
Renyong Jia
Yaqin Chen
Hao Zhou
Hao Zhou
Xu Song
author_sort Huaiyue Hu
collection DOAJ
description Myricetin, a polyhydroxyflavone compound, is one of the main ingredients of various human foods and therefore also known as dietary flavonoids. Due to the continuous emergence of resistant strains of herpesviruses, novel control measures are required. In the present study, myricetin exhibited potent antiviral activity against pseudorabies virus (PRV), a model organism of herpesvirus. The suppression rate could reach up to 96.4% at a concentration of 500 μM in cells, and the 50% inhibitory concentration (IC50) was 42.69 μM. Moreover, the inhibitory activity was not attenuated by the increased amount of infective dose, and a significant reduction of intracellular PRV virions was observed by indirect immunofluorescence. A mode of action study indicated that myricetin could directly inactivate the virus in vitro, leading to inhibition of viral adsorption, penetration and replication in cells. In addition to direct killing effect, myricetin could also activate host antiviral defense through regulation of apoptosis-related gene expressions (Bcl-2, Bcl-xl, Bax), NF-κB and MAPK signaling pathways and cytokine gene expressions (IL-1α, IL-1β, IL-6, c-Jun, STAT1, c-Fos, and c-Myc). In PRV-infected mouse model, myricetin could enhance the survival rate by 40% at 5 days post infection, and viral loads in kidney, liver, lung, spleen, and brain were significantly decreased. The pathological changes caused by PRV infection were improved by myricetin treatment. The gene expressions of inflammatory factors (MCP-1, G-CSF, IL-1α, IL-1β, and IL-6) and apoptotic factors (Bcl-xl, Bcl-2, and Bax) were regulated by myricetin in PRV-infected mice. The present findings suggest that myricetin can effectively inhibit PRV infection and become a candidate for development of new anti-herpesvirus drugs.
first_indexed 2024-04-11T20:35:49Z
format Article
id doaj.art-1a470fc198574ef9a0f2951b7f808c76
institution Directory Open Access Journal
issn 1664-302X
language English
last_indexed 2024-04-11T20:35:49Z
publishDate 2022-09-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Microbiology
spelling doaj.art-1a470fc198574ef9a0f2951b7f808c762022-12-22T04:04:22ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-09-011310.3389/fmicb.2022.985108985108Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defenseHuaiyue Hu0Zhiqiang Hu1Yingying Zhang2Hongping Wan3Zhongqiong Yin4Lixia Li5Xiaoxia Liang6Xinghong Zhao7Lizi Yin8Gang Ye9Yuan-Feng Zou10Huaqiao Tang11Renyong Jia12Yaqin Chen13Hao Zhou14Hao Zhou15Xu Song16Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaShandong New Hope Liuhe Agriculture and Animal Husbandry Technology Co., Ltd., Dezhou, ChinaCollege of Animal Science and Technology, Sichuan Agricultural University, Chengdu, ChinaNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Microbiology, NYU Grossman School of Medicine, New York, NY, United StatesNatural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaMyricetin, a polyhydroxyflavone compound, is one of the main ingredients of various human foods and therefore also known as dietary flavonoids. Due to the continuous emergence of resistant strains of herpesviruses, novel control measures are required. In the present study, myricetin exhibited potent antiviral activity against pseudorabies virus (PRV), a model organism of herpesvirus. The suppression rate could reach up to 96.4% at a concentration of 500 μM in cells, and the 50% inhibitory concentration (IC50) was 42.69 μM. Moreover, the inhibitory activity was not attenuated by the increased amount of infective dose, and a significant reduction of intracellular PRV virions was observed by indirect immunofluorescence. A mode of action study indicated that myricetin could directly inactivate the virus in vitro, leading to inhibition of viral adsorption, penetration and replication in cells. In addition to direct killing effect, myricetin could also activate host antiviral defense through regulation of apoptosis-related gene expressions (Bcl-2, Bcl-xl, Bax), NF-κB and MAPK signaling pathways and cytokine gene expressions (IL-1α, IL-1β, IL-6, c-Jun, STAT1, c-Fos, and c-Myc). In PRV-infected mouse model, myricetin could enhance the survival rate by 40% at 5 days post infection, and viral loads in kidney, liver, lung, spleen, and brain were significantly decreased. The pathological changes caused by PRV infection were improved by myricetin treatment. The gene expressions of inflammatory factors (MCP-1, G-CSF, IL-1α, IL-1β, and IL-6) and apoptotic factors (Bcl-xl, Bcl-2, and Bax) were regulated by myricetin in PRV-infected mice. The present findings suggest that myricetin can effectively inhibit PRV infection and become a candidate for development of new anti-herpesvirus drugs.https://www.frontiersin.org/articles/10.3389/fmicb.2022.985108/fullmyricetindietary flavonoidsherpesviruspseudorabies virusantiviral activity
spellingShingle Huaiyue Hu
Zhiqiang Hu
Yingying Zhang
Hongping Wan
Zhongqiong Yin
Lixia Li
Xiaoxia Liang
Xinghong Zhao
Lizi Yin
Gang Ye
Yuan-Feng Zou
Huaqiao Tang
Renyong Jia
Yaqin Chen
Hao Zhou
Hao Zhou
Xu Song
Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense
Frontiers in Microbiology
myricetin
dietary flavonoids
herpesvirus
pseudorabies virus
antiviral activity
title Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense
title_full Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense
title_fullStr Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense
title_full_unstemmed Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense
title_short Myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense
title_sort myricetin inhibits pseudorabies virus infection through direct inactivation and activating host antiviral defense
topic myricetin
dietary flavonoids
herpesvirus
pseudorabies virus
antiviral activity
url https://www.frontiersin.org/articles/10.3389/fmicb.2022.985108/full
work_keys_str_mv AT huaiyuehu myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT zhiqianghu myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT yingyingzhang myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT hongpingwan myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT zhongqiongyin myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT lixiali myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT xiaoxialiang myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT xinghongzhao myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT liziyin myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT gangye myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT yuanfengzou myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT huaqiaotang myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT renyongjia myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT yaqinchen myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT haozhou myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT haozhou myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense
AT xusong myricetininhibitspseudorabiesvirusinfectionthroughdirectinactivationandactivatinghostantiviraldefense