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Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication
The interferon-induced double-strand RNA activated protein kinase (PKR) plays important roles in host defense against viral infection. Here we demonstrate the significant antiviral role of PKR against foot-and-mouth disease virus (FMDV) and report that FMDV infection inhibits PKR expression and acti...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126777/ https://www.ncbi.nlm.nih.gov/pubmed/28662438 http://dx.doi.org/10.1016/j.virol.2017.06.023 |
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author | Li, Chuntian Zhu, Zixiang Du, Xiaoli Cao, Weijun Yang, Fan Zhang, Xiangle Feng, Huanhuan Li, Dan Zhang, Keshan Liu, Xiangtao Zheng, Haixue |
author_facet | Li, Chuntian Zhu, Zixiang Du, Xiaoli Cao, Weijun Yang, Fan Zhang, Xiangle Feng, Huanhuan Li, Dan Zhang, Keshan Liu, Xiangtao Zheng, Haixue |
author_sort | Li, Chuntian |
collection | PubMed |
description | The interferon-induced double-strand RNA activated protein kinase (PKR) plays important roles in host defense against viral infection. Here we demonstrate the significant antiviral role of PKR against foot-and-mouth disease virus (FMDV) and report that FMDV infection inhibits PKR expression and activation in porcine kidney (PK-15) cells. The viral nonstructural protein 3 C proteinase (3C(pro)) is identified to be responsible for this inhibition. However, it is independent of the well-known proteinase activity of 3C(pro) or 3C(pro)-induced shutoff of host protein synthesis. We show that 3C(pro) induces PKR degradation by lysosomal pathway and no interaction is determined between 3C(pro) and PKR. Together, our results indicate that PKR acts an important antiviral factor during FMDV infection, and FMDV has evolved a strategy to overcome PKR-mediated antiviral role by downregulation of PKR protein. |
format | Online Article Text |
id | pubmed-7126777 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71267772020-04-08 Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication Li, Chuntian Zhu, Zixiang Du, Xiaoli Cao, Weijun Yang, Fan Zhang, Xiangle Feng, Huanhuan Li, Dan Zhang, Keshan Liu, Xiangtao Zheng, Haixue Virology Article The interferon-induced double-strand RNA activated protein kinase (PKR) plays important roles in host defense against viral infection. Here we demonstrate the significant antiviral role of PKR against foot-and-mouth disease virus (FMDV) and report that FMDV infection inhibits PKR expression and activation in porcine kidney (PK-15) cells. The viral nonstructural protein 3 C proteinase (3C(pro)) is identified to be responsible for this inhibition. However, it is independent of the well-known proteinase activity of 3C(pro) or 3C(pro)-induced shutoff of host protein synthesis. We show that 3C(pro) induces PKR degradation by lysosomal pathway and no interaction is determined between 3C(pro) and PKR. Together, our results indicate that PKR acts an important antiviral factor during FMDV infection, and FMDV has evolved a strategy to overcome PKR-mediated antiviral role by downregulation of PKR protein. Elsevier Inc. 2017-09 2017-06-26 /pmc/articles/PMC7126777/ /pubmed/28662438 http://dx.doi.org/10.1016/j.virol.2017.06.023 Text en © 2017 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Li, Chuntian Zhu, Zixiang Du, Xiaoli Cao, Weijun Yang, Fan Zhang, Xiangle Feng, Huanhuan Li, Dan Zhang, Keshan Liu, Xiangtao Zheng, Haixue Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication |
title | Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication |
title_full | Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication |
title_fullStr | Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication |
title_full_unstemmed | Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication |
title_short | Foot-and-mouth disease virus induces lysosomal degradation of host protein kinase PKR by 3C proteinase to facilitate virus replication |
title_sort | foot-and-mouth disease virus induces lysosomal degradation of host protein kinase pkr by 3c proteinase to facilitate virus replication |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126777/ https://www.ncbi.nlm.nih.gov/pubmed/28662438 http://dx.doi.org/10.1016/j.virol.2017.06.023 |
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