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Induction of UPR Promotes Interferon Response to Inhibit PRRSV Replication via PKR and NF-κB Pathway

Porcine reproductive and respiratory syndrome virus (PRRSV) was previously shown to induce a certain level of cellular stress during viral replication. Unfolded protein response (UPR) is a cellular stress response responsible for coping with stress and cellular survival. However, the pathway leading...

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Autores principales: Zhu, Zhenbang, Liu, Panrao, Yuan, Lili, Lian, Zhengmin, Hu, Danhe, Yao, Xiaohui, Li, Xiangdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547762/
https://www.ncbi.nlm.nih.gov/pubmed/34712218
http://dx.doi.org/10.3389/fmicb.2021.757690
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author Zhu, Zhenbang
Liu, Panrao
Yuan, Lili
Lian, Zhengmin
Hu, Danhe
Yao, Xiaohui
Li, Xiangdong
author_facet Zhu, Zhenbang
Liu, Panrao
Yuan, Lili
Lian, Zhengmin
Hu, Danhe
Yao, Xiaohui
Li, Xiangdong
author_sort Zhu, Zhenbang
collection PubMed
description Porcine reproductive and respiratory syndrome virus (PRRSV) was previously shown to induce a certain level of cellular stress during viral replication. Unfolded protein response (UPR) is a cellular stress response responsible for coping with stress and cellular survival. However, the pathway leading to the induction of UPR that may influence PRRSV replication is still unknown. Here, we found that PRRSV infection induced UPR prior to interferon response. Induction of UPR significantly enhanced the expression of interferon and interferon-related genes, thus leading to the suppression of PRRSV infection. Next, we explored the underlying mechanisms of UPR-induced antiviral response. We found that induction of UPR promoted the expression of protein kinase R (PKR), and PKR was highly correlated with the reduction of PRRSV replication. Furthermore, tunicamycin stimulation and PKR overexpression activated NF-κB and interferon response at the early stage of PRRSV infection, thus reinforcing the expression of type I interferons and proinflammatory cytokines and leading to inhibition of PRRSV. In addition, PRRSV nsp4 was shown to reduce the expression of PKR. These findings might have implications for our understandings of the host’s immune mechanism against PRRSV and a new strategy of PRRSV to evade the host antiviral immunity.
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spelling pubmed-85477622021-10-27 Induction of UPR Promotes Interferon Response to Inhibit PRRSV Replication via PKR and NF-κB Pathway Zhu, Zhenbang Liu, Panrao Yuan, Lili Lian, Zhengmin Hu, Danhe Yao, Xiaohui Li, Xiangdong Front Microbiol Microbiology Porcine reproductive and respiratory syndrome virus (PRRSV) was previously shown to induce a certain level of cellular stress during viral replication. Unfolded protein response (UPR) is a cellular stress response responsible for coping with stress and cellular survival. However, the pathway leading to the induction of UPR that may influence PRRSV replication is still unknown. Here, we found that PRRSV infection induced UPR prior to interferon response. Induction of UPR significantly enhanced the expression of interferon and interferon-related genes, thus leading to the suppression of PRRSV infection. Next, we explored the underlying mechanisms of UPR-induced antiviral response. We found that induction of UPR promoted the expression of protein kinase R (PKR), and PKR was highly correlated with the reduction of PRRSV replication. Furthermore, tunicamycin stimulation and PKR overexpression activated NF-κB and interferon response at the early stage of PRRSV infection, thus reinforcing the expression of type I interferons and proinflammatory cytokines and leading to inhibition of PRRSV. In addition, PRRSV nsp4 was shown to reduce the expression of PKR. These findings might have implications for our understandings of the host’s immune mechanism against PRRSV and a new strategy of PRRSV to evade the host antiviral immunity. Frontiers Media S.A. 2021-10-12 /pmc/articles/PMC8547762/ /pubmed/34712218 http://dx.doi.org/10.3389/fmicb.2021.757690 Text en Copyright © 2021 Zhu, Liu, Yuan, Lian, Hu, Yao and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Zhu, Zhenbang
Liu, Panrao
Yuan, Lili
Lian, Zhengmin
Hu, Danhe
Yao, Xiaohui
Li, Xiangdong
Induction of UPR Promotes Interferon Response to Inhibit PRRSV Replication via PKR and NF-κB Pathway
title Induction of UPR Promotes Interferon Response to Inhibit PRRSV Replication via PKR and NF-κB Pathway
title_full Induction of UPR Promotes Interferon Response to Inhibit PRRSV Replication via PKR and NF-κB Pathway
title_fullStr Induction of UPR Promotes Interferon Response to Inhibit PRRSV Replication via PKR and NF-κB Pathway
title_full_unstemmed Induction of UPR Promotes Interferon Response to Inhibit PRRSV Replication via PKR and NF-κB Pathway
title_short Induction of UPR Promotes Interferon Response to Inhibit PRRSV Replication via PKR and NF-κB Pathway
title_sort induction of upr promotes interferon response to inhibit prrsv replication via pkr and nf-κb pathway
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547762/
https://www.ncbi.nlm.nih.gov/pubmed/34712218
http://dx.doi.org/10.3389/fmicb.2021.757690
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