Mechanism of selenomethionine inhibiting of PDCoV replication in LLC-PK1 cells based on STAT3/miR-125b-5p-1/HK2 signaling

There are no licensed therapeutics or vaccines available against porcine delta coronavirus (PDCoV) to eliminate its potential for congenital disease. In the absence of effective treatments, it has led to significant economic losses in the swine industry worldwide. Similar to the current coronavirus...

Full description

Bibliographic Details
Main Authors: Zhihua Ren, Ting Ding, Hongyi He, Zhanyong Wei, Riyi Shi, Junliang Deng
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.952852/full
_version_ 1811339822682341376
author Zhihua Ren
Zhihua Ren
Ting Ding
Hongyi He
Zhanyong Wei
Riyi Shi
Junliang Deng
author_facet Zhihua Ren
Zhihua Ren
Ting Ding
Hongyi He
Zhanyong Wei
Riyi Shi
Junliang Deng
author_sort Zhihua Ren
collection DOAJ
description There are no licensed therapeutics or vaccines available against porcine delta coronavirus (PDCoV) to eliminate its potential for congenital disease. In the absence of effective treatments, it has led to significant economic losses in the swine industry worldwide. Similar to the current coronavirus disease 2019 (COVID-19) pandemic, PDCoV is trans-species transmissible and there is still a large desert for scientific exploration. We have reported that selenomethionine (SeMet) has potent antiviral activity against PDCoV. Here, we systematically investigated the endogenous immune mechanism of SeMet and found that STAT3/miR-125b-5p-1/HK2 signalling is essential for the exertion of SeMet anti-PDCoV replication function. Meanwhile, HK2, a key rate-limiting enzyme of the glycolytic pathway, was able to control PDCoV replication in LLC-PK1 cells, suggesting a strategy for viruses to evade innate immunity using glucose metabolism pathways. Overall, based on the ability of selenomethionine to control PDCoV infection and transmission, we provide a molecular basis for the development of new therapeutic approaches.
first_indexed 2024-04-13T18:33:10Z
format Article
id doaj.art-58503122c4de44d4a697773d35659012
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-04-13T18:33:10Z
publishDate 2022-08-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-58503122c4de44d4a697773d356590122022-12-22T02:35:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.952852952852Mechanism of selenomethionine inhibiting of PDCoV replication in LLC-PK1 cells based on STAT3/miR-125b-5p-1/HK2 signalingZhihua Ren0Zhihua Ren1Ting Ding2Hongyi He3Zhanyong Wei4Riyi Shi5Junliang Deng6College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou, ChinaDepartment of Basic Medical Sciences, College of Veterinary Medicine, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United StatesKey Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, ChinaThere are no licensed therapeutics or vaccines available against porcine delta coronavirus (PDCoV) to eliminate its potential for congenital disease. In the absence of effective treatments, it has led to significant economic losses in the swine industry worldwide. Similar to the current coronavirus disease 2019 (COVID-19) pandemic, PDCoV is trans-species transmissible and there is still a large desert for scientific exploration. We have reported that selenomethionine (SeMet) has potent antiviral activity against PDCoV. Here, we systematically investigated the endogenous immune mechanism of SeMet and found that STAT3/miR-125b-5p-1/HK2 signalling is essential for the exertion of SeMet anti-PDCoV replication function. Meanwhile, HK2, a key rate-limiting enzyme of the glycolytic pathway, was able to control PDCoV replication in LLC-PK1 cells, suggesting a strategy for viruses to evade innate immunity using glucose metabolism pathways. Overall, based on the ability of selenomethionine to control PDCoV infection and transmission, we provide a molecular basis for the development of new therapeutic approaches.https://www.frontiersin.org/articles/10.3389/fimmu.2022.952852/fullPDCoVSeMetSTAT3miR-125b-5p-1HK2
spellingShingle Zhihua Ren
Zhihua Ren
Ting Ding
Hongyi He
Zhanyong Wei
Riyi Shi
Junliang Deng
Mechanism of selenomethionine inhibiting of PDCoV replication in LLC-PK1 cells based on STAT3/miR-125b-5p-1/HK2 signaling
Frontiers in Immunology
PDCoV
SeMet
STAT3
miR-125b-5p-1
HK2
title Mechanism of selenomethionine inhibiting of PDCoV replication in LLC-PK1 cells based on STAT3/miR-125b-5p-1/HK2 signaling
title_full Mechanism of selenomethionine inhibiting of PDCoV replication in LLC-PK1 cells based on STAT3/miR-125b-5p-1/HK2 signaling
title_fullStr Mechanism of selenomethionine inhibiting of PDCoV replication in LLC-PK1 cells based on STAT3/miR-125b-5p-1/HK2 signaling
title_full_unstemmed Mechanism of selenomethionine inhibiting of PDCoV replication in LLC-PK1 cells based on STAT3/miR-125b-5p-1/HK2 signaling
title_short Mechanism of selenomethionine inhibiting of PDCoV replication in LLC-PK1 cells based on STAT3/miR-125b-5p-1/HK2 signaling
title_sort mechanism of selenomethionine inhibiting of pdcov replication in llc pk1 cells based on stat3 mir 125b 5p 1 hk2 signaling
topic PDCoV
SeMet
STAT3
miR-125b-5p-1
HK2
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.952852/full
work_keys_str_mv AT zhihuaren mechanismofselenomethionineinhibitingofpdcovreplicationinllcpk1cellsbasedonstat3mir125b5p1hk2signaling
AT zhihuaren mechanismofselenomethionineinhibitingofpdcovreplicationinllcpk1cellsbasedonstat3mir125b5p1hk2signaling
AT tingding mechanismofselenomethionineinhibitingofpdcovreplicationinllcpk1cellsbasedonstat3mir125b5p1hk2signaling
AT hongyihe mechanismofselenomethionineinhibitingofpdcovreplicationinllcpk1cellsbasedonstat3mir125b5p1hk2signaling
AT zhanyongwei mechanismofselenomethionineinhibitingofpdcovreplicationinllcpk1cellsbasedonstat3mir125b5p1hk2signaling
AT riyishi mechanismofselenomethionineinhibitingofpdcovreplicationinllcpk1cellsbasedonstat3mir125b5p1hk2signaling
AT junliangdeng mechanismofselenomethionineinhibitingofpdcovreplicationinllcpk1cellsbasedonstat3mir125b5p1hk2signaling