PCV2 and PRV Coinfection Induces Endoplasmic Reticulum Stress via PERK-eIF2α-ATF4-CHOP and IRE1-XBP1-EDEM Pathways

Porcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are two important pathogens in the pig industry. PCV2 or PRV infection can induce endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). However, the effect of PCV2 and PRV coinfection on the ERS and UPR pathways remains uncle...

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Main Authors: Si Chen, Xue Li, Xinwei Zhang, Guyu Niu, Lin Yang, Weilong Ji, Liying Zhang, Linzhu Ren
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/9/4479
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author Si Chen
Xue Li
Xinwei Zhang
Guyu Niu
Lin Yang
Weilong Ji
Liying Zhang
Linzhu Ren
author_facet Si Chen
Xue Li
Xinwei Zhang
Guyu Niu
Lin Yang
Weilong Ji
Liying Zhang
Linzhu Ren
author_sort Si Chen
collection DOAJ
description Porcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are two important pathogens in the pig industry. PCV2 or PRV infection can induce endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). However, the effect of PCV2 and PRV coinfection on the ERS and UPR pathways remains unclear. In this study, we found that PRV inhibited the proliferation of PCV2 mainly at 36 to 72 hpi, while PCV2 enhanced the proliferation of PRV in the middle stage of the infection. Notably, PRV is the main factor during coinfection. The results of the transcriptomic analysis showed that coinfection with PCV2 and PRV activated cellular ERS, and upregulated expressions of the ERS pathway-related proteins, including GRP78, eIF2α, and ATF4. Further research indicated that PRV played a dominant role in the sequential infection and coinfection of PCV2 and PRV. PCV2 and PRV coinfection induced the ERS activation via the PERK-eIF2α-ATF4-CHOP axis and IRE1-XBP1-EDEM pathway, and thus may enhance cell apoptosis and exacerbate the diseases.
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spelling doaj.art-8fe9b4572d16406c8b754c4ea0c193632023-11-23T08:17:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239447910.3390/ijms23094479PCV2 and PRV Coinfection Induces Endoplasmic Reticulum Stress via PERK-eIF2α-ATF4-CHOP and IRE1-XBP1-EDEM PathwaysSi Chen0Xue Li1Xinwei Zhang2Guyu Niu3Lin Yang4Weilong Ji5Liying Zhang6Linzhu Ren7College of Animal Sciences, Key Lab for Zoonoses Research, Ministry of Education, Jilin University, 5333 Xi’an Road, Changchun 130062, ChinaCollege of Animal Sciences, Key Lab for Zoonoses Research, Ministry of Education, Jilin University, 5333 Xi’an Road, Changchun 130062, ChinaCollege of Animal Sciences, Key Lab for Zoonoses Research, Ministry of Education, Jilin University, 5333 Xi’an Road, Changchun 130062, ChinaCollege of Animal Sciences, Key Lab for Zoonoses Research, Ministry of Education, Jilin University, 5333 Xi’an Road, Changchun 130062, ChinaCollege of Animal Sciences, Key Lab for Zoonoses Research, Ministry of Education, Jilin University, 5333 Xi’an Road, Changchun 130062, ChinaCollege of Animal Sciences, Key Lab for Zoonoses Research, Ministry of Education, Jilin University, 5333 Xi’an Road, Changchun 130062, ChinaCollege of Animal Sciences, Key Lab for Zoonoses Research, Ministry of Education, Jilin University, 5333 Xi’an Road, Changchun 130062, ChinaCollege of Animal Sciences, Key Lab for Zoonoses Research, Ministry of Education, Jilin University, 5333 Xi’an Road, Changchun 130062, ChinaPorcine circovirus 2 (PCV2) and pseudorabies virus (PRV) are two important pathogens in the pig industry. PCV2 or PRV infection can induce endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). However, the effect of PCV2 and PRV coinfection on the ERS and UPR pathways remains unclear. In this study, we found that PRV inhibited the proliferation of PCV2 mainly at 36 to 72 hpi, while PCV2 enhanced the proliferation of PRV in the middle stage of the infection. Notably, PRV is the main factor during coinfection. The results of the transcriptomic analysis showed that coinfection with PCV2 and PRV activated cellular ERS, and upregulated expressions of the ERS pathway-related proteins, including GRP78, eIF2α, and ATF4. Further research indicated that PRV played a dominant role in the sequential infection and coinfection of PCV2 and PRV. PCV2 and PRV coinfection induced the ERS activation via the PERK-eIF2α-ATF4-CHOP axis and IRE1-XBP1-EDEM pathway, and thus may enhance cell apoptosis and exacerbate the diseases.https://www.mdpi.com/1422-0067/23/9/4479porcine circovirus type 2porcine pseudorabies viruscoinfectionendoplasmic reticulum stress (ERS)transcriptome sequencing
spellingShingle Si Chen
Xue Li
Xinwei Zhang
Guyu Niu
Lin Yang
Weilong Ji
Liying Zhang
Linzhu Ren
PCV2 and PRV Coinfection Induces Endoplasmic Reticulum Stress via PERK-eIF2α-ATF4-CHOP and IRE1-XBP1-EDEM Pathways
International Journal of Molecular Sciences
porcine circovirus type 2
porcine pseudorabies virus
coinfection
endoplasmic reticulum stress (ERS)
transcriptome sequencing
title PCV2 and PRV Coinfection Induces Endoplasmic Reticulum Stress via PERK-eIF2α-ATF4-CHOP and IRE1-XBP1-EDEM Pathways
title_full PCV2 and PRV Coinfection Induces Endoplasmic Reticulum Stress via PERK-eIF2α-ATF4-CHOP and IRE1-XBP1-EDEM Pathways
title_fullStr PCV2 and PRV Coinfection Induces Endoplasmic Reticulum Stress via PERK-eIF2α-ATF4-CHOP and IRE1-XBP1-EDEM Pathways
title_full_unstemmed PCV2 and PRV Coinfection Induces Endoplasmic Reticulum Stress via PERK-eIF2α-ATF4-CHOP and IRE1-XBP1-EDEM Pathways
title_short PCV2 and PRV Coinfection Induces Endoplasmic Reticulum Stress via PERK-eIF2α-ATF4-CHOP and IRE1-XBP1-EDEM Pathways
title_sort pcv2 and prv coinfection induces endoplasmic reticulum stress via perk eif2α atf4 chop and ire1 xbp1 edem pathways
topic porcine circovirus type 2
porcine pseudorabies virus
coinfection
endoplasmic reticulum stress (ERS)
transcriptome sequencing
url https://www.mdpi.com/1422-0067/23/9/4479
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