PMID- 38499512
OWN - NLM
STAT- MEDLINE
DCOM- 20240417
LR  - 20240426
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 98
IP  - 4
DP  - 2024 Apr 16
TI  - Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN 
      production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways.
PG  - e0015924
LID - 10.1128/jvi.00159-24 [doi]
LID - e00159-24
AB  - 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.
FAU - Wang, Tongtong
AU  - Wang T
AD  - College of Agronomy, Liaocheng University, Liaocheng, China.
FAU - Hu, Leyu
AU  - Hu L
AD  - College of Agronomy, Liaocheng University, Liaocheng, China.
AD  - College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, China.
FAU - Li, Ruibo
AU  - Li R
AD  - College of Agronomy, Liaocheng University, Liaocheng, China.
FAU - Ren, Huiying
AU  - Ren H
AD  - College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, China.
FAU - Li, Shuwen
AU  - Li S
AD  - College of Agronomy, Liaocheng University, Liaocheng, China.
FAU - Sun, Qi
AU  - Sun Q
AD  - College of Agronomy, Liaocheng University, Liaocheng, China.
FAU - Ding, Xiangdan
AU  - Ding X
AD  - College of Agronomy, Liaocheng University, Liaocheng, China.
FAU - Li, Yubao
AU  - Li Y
AUID- ORCID: 0000-0002-8533-5015
AD  - College of Agronomy, Liaocheng University, Liaocheng, China.
FAU - Wang, Changfa
AU  - Wang C
AUID- ORCID: 0000-0002-5186-1703
AD  - College of Agronomy, Liaocheng University, Liaocheng, China.
FAU - Li, Liangliang
AU  - Li L
AUID- ORCID: 0000-0001-5431-9103
AD  - College of Agronomy, Liaocheng University, Liaocheng, China.
LA  - eng
GR  - 32002248/MOST | National Natural Science Foundation of China (NSFC)/
GR  - ZR2020QC016/| Natural Science Foundation of Shandong Province ()/
GR  - ZR2020QC017/| Natural Science Foundation of Shandong Province ()/
PT  - Journal Article
DEP - 20240319
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antiviral Agents)
RN  - 8O1CR18L82 (hyperoside)
RN  - 9008-11-1 (Interferons)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 9IKM0I5T1E (Quercetin)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Mice
MH  - Rabbits
MH  - *Antiviral Agents/pharmacology
MH  - *Herpesviridae Infections
MH  - *Herpesvirus 1, Equid
MH  - Horses
MH  - Interferons/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Kelch-Like ECH-Associated Protein 1/metabolism
MH  - *MAP Kinase Signaling System
MH  - NF-E2-Related Factor 2/metabolism
MH  - Oxidative Stress/drug effects
MH  - *Quercetin/analogs & derivatives/pharmacology
MH  - Cell Line
PMC - PMC11019850
OTO - NOTNLM
OT  - EHV-8 inhibitor
OT  - IFN response
OT  - JNK/Nrf2/ Keap1/HO-1
OT  - antioxidants
OT  - hyperoside
COIS- The authors declare no conflict of interest.
EDAT- 2024/03/19 06:43
MHDA- 2024/04/17 06:43
PMCR- 2024/03/19
CRDT- 2024/03/19 00:03
PHST- 2024/04/17 06:43 [medline]
PHST- 2024/03/19 06:43 [pubmed]
PHST- 2024/03/19 00:03 [entrez]
PHST- 2024/03/19 00:00 [pmc-release]
AID - 00159-24 [pii]
AID - jvi.00159-24 [pii]
AID - 10.1128/jvi.00159-24 [doi]
PST - ppublish
SO  - J Virol. 2024 Apr 16;98(4):e0015924. doi: 10.1128/jvi.00159-24. Epub 2024 Mar 19.