PMID- 37239983
OWN - NLM
STAT- MEDLINE
DCOM- 20230529
LR  - 20230529
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 10
DP  - 2023 May 12
TI  - Ethyl Gallate Inhibits Bovine Viral Diarrhea Virus by Promoting IFITM3 
      Expression, Lysosomal Acidification and Protease Activity.
LID - 10.3390/ijms24108637 [doi]
LID - 8637
AB  - Bovine viral diarrhea virus (BVDV) is a highly contagious viral disease which 
      causes economic losses to the cattle industry. Ethyl gallate (EG) is a phenolic 
      acid derivative which has various potentials to modulate the host response to 
      pathogens, such as via antioxidant activity, antibacterial activity, inhibition 
      of the production of cell adhesion factors, and so on. This study aimed to 
      evaluate if EG influences BVDV infection in Madin-Darby Bovine Kidney (MDBK) 
      cells, and to understand the antiviral mechanism. Data indicated that EG 
      effectively inhibited BVDV infection by co-treatment and post-treatment in MDBK 
      cells with noncytotoxic doses. In addition, EG suppressed BVDV infection at an 
      early stage of the viral life cycle by blocking entry and replication steps but 
      not viral attachment and release. Moreover, EG strongly inhibited BVDV infection 
      by promoting interferon-induced transmembrane protein 3 (IFITM3) expression, 
      which localized to the cytoplasm. The protein level of cathepsin B was 
      significantly reduced by BVDV infection, whereas with treatment with EG, it was 
      significantly enhanced. The fluorescence intensities of acridine orange (AO) 
      staining were significantly decreased in BVDV-infected cells but increased in 
      EG-treated cells. Finally, Western blot and immunofluorescence analyses 
      demonstrated that EG treatment significantly enhanced the protein levels of 
      autophagy markers LC3 and p62. Chloroquine (CQ) significantly increased IFITM3 
      expression, and Rapamycin significantly decreased it. Thus, EG may regulate 
      IFITM3 expression through autophagy. Our results showed that EG could have a 
      solid antiviral activity on BVDV replication in MDBK cells via increased IFITM3 
      expression, lysosomal acidification, protease activity, and regulated autophagy. 
      EG might have value for further development as an antiviral agent.
FAU - Zhang, Linlin
AU  - Zhang L
AD  - College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan 
      West Road, Beijing 100193, China.
FAU - Yang, Guanghui
AU  - Yang G
AUID- ORCID: 0000-0003-4652-6166
AD  - College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan 
      West Road, Beijing 100193, China.
FAU - Wang, Jun
AU  - Wang J
AD  - College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan 
      West Road, Beijing 100193, China.
FAU - Zhang, Jialu
AU  - Zhang J
AD  - College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan 
      West Road, Beijing 100193, China.
FAU - Chen, Keyuan
AU  - Chen K
AD  - College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan 
      West Road, Beijing 100193, China.
FAU - Xiong, Xiaoran
AU  - Xiong X
AD  - College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan 
      West Road, Beijing 100193, China.
FAU - Zhu, Yaohong
AU  - Zhu Y
AD  - College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan 
      West Road, Beijing 100193, China.
FAU - Xu, Chuang
AU  - Xu C
AD  - College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan 
      West Road, Beijing 100193, China.
FAU - Wang, Jiufeng
AU  - Wang J
AUID- ORCID: 0000-0002-0183-5611
AD  - College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan 
      West Road, Beijing 100193, China.
LA  - eng
GR  - No. ZDYF2023XDNY038/Jiufeng Wang/
GR  - No. 2017YFD0502204/Jiufeng Wang/
PT  - Journal Article
DEP - 20230512
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 235I6UDD3L (ethyl gallate)
RN  - 0 (Antiviral Agents)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cell Line
MH  - *Virus Replication
MH  - *Diarrhea Viruses, Bovine Viral/metabolism
MH  - Antiviral Agents/pharmacology/metabolism
MH  - Hydrogen-Ion Concentration
MH  - Diarrhea
MH  - Lysosomes
MH  - Peptide Hydrolases/metabolism
PMC - PMC10218043
OTO - NOTNLM
OT  - BVDV
OT  - IFITM3
OT  - antiviral
OT  - autophagy
OT  - ethyl gallate
OT  - lysosomal acidification
COIS- The authors declare no conflict of interest.
EDAT- 2023/05/27 09:42
MHDA- 2023/05/29 06:41
PMCR- 2023/05/12
CRDT- 2023/05/27 01:14
PHST- 2023/04/10 00:00 [received]
PHST- 2023/05/03 00:00 [revised]
PHST- 2023/05/06 00:00 [accepted]
PHST- 2023/05/29 06:41 [medline]
PHST- 2023/05/27 09:42 [pubmed]
PHST- 2023/05/27 01:14 [entrez]
PHST- 2023/05/12 00:00 [pmc-release]
AID - ijms24108637 [pii]
AID - ijms-24-08637 [pii]
AID - 10.3390/ijms24108637 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 May 12;24(10):8637. doi: 10.3390/ijms24108637.