Porcine reproductive and respiratory syndrome virus nonstructural protein 4 induces apoptosis dependent on its 3C-like serine protease activity.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease in pigs caused by PRRS virus (PRRSV). Although PRRSV infection-induced cell apoptosis has been established, the related viral protein is still unknown. Here, we reported that PRRSV nonstructural protein 4 (nsp4) was...

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Autores principales: Zhitao Ma, Yalan Wang, Haiyan Zhao, Ao-Tian Xu, Yongqiang Wang, Jun Tang, Wen-hai Feng
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/b7e6535335fe43eaa6baf8b3e6b35c1a
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spelling oai:doaj.org-article:b7e6535335fe43eaa6baf8b3e6b35c1a2021-11-18T09:03:18ZPorcine reproductive and respiratory syndrome virus nonstructural protein 4 induces apoptosis dependent on its 3C-like serine protease activity.1932-620310.1371/journal.pone.0069387https://doaj.org/article/b7e6535335fe43eaa6baf8b3e6b35c1a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936003/?tool=EBIhttps://doaj.org/toc/1932-6203Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease in pigs caused by PRRS virus (PRRSV). Although PRRSV infection-induced cell apoptosis has been established, the related viral protein is still unknown. Here, we reported that PRRSV nonstructural protein 4 (nsp4) was a critical apoptosis inducer. Nsp4 could activate caspase-3, -8, and -9. Using truncated constructs without different domains in nsp4, we demonstrated that the full-length of nsp4 structure was required for its apoptosis-inducing activity. Furthermore, using site-directed mutagenesis to inactivate the 3C-like serine protease activity of nsp4, we showed that nsp4-induced apoptosis was dependent on its serine protease activity. The ability of nsp4 to induce apoptosis was significantly impaired by His39, Asp64, and Ser118 mutations, suggesting that His39, Asp64, and Ser118 were essential for nsp4 to trigger apoptosis. In conclusion, our present work showed that PRRSV nsp4 could induce apoptosis in host cells and might be partially responsible for the apoptosis induced by PRRSV infection. PRRSV 3C-like protease-mediated apoptosis represents the first report in the genus Arterivirus, family Arteriviridae.Zhitao MaYalan WangHaiyan ZhaoAo-Tian XuYongqiang WangJun TangWen-hai FengPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69387 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Zhitao Ma
Yalan Wang
Haiyan Zhao
Ao-Tian Xu
Yongqiang Wang
Jun Tang
Wen-hai Feng
Porcine reproductive and respiratory syndrome virus nonstructural protein 4 induces apoptosis dependent on its 3C-like serine protease activity.
description Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease in pigs caused by PRRS virus (PRRSV). Although PRRSV infection-induced cell apoptosis has been established, the related viral protein is still unknown. Here, we reported that PRRSV nonstructural protein 4 (nsp4) was a critical apoptosis inducer. Nsp4 could activate caspase-3, -8, and -9. Using truncated constructs without different domains in nsp4, we demonstrated that the full-length of nsp4 structure was required for its apoptosis-inducing activity. Furthermore, using site-directed mutagenesis to inactivate the 3C-like serine protease activity of nsp4, we showed that nsp4-induced apoptosis was dependent on its serine protease activity. The ability of nsp4 to induce apoptosis was significantly impaired by His39, Asp64, and Ser118 mutations, suggesting that His39, Asp64, and Ser118 were essential for nsp4 to trigger apoptosis. In conclusion, our present work showed that PRRSV nsp4 could induce apoptosis in host cells and might be partially responsible for the apoptosis induced by PRRSV infection. PRRSV 3C-like protease-mediated apoptosis represents the first report in the genus Arterivirus, family Arteriviridae.
format article
author Zhitao Ma
Yalan Wang
Haiyan Zhao
Ao-Tian Xu
Yongqiang Wang
Jun Tang
Wen-hai Feng
author_facet Zhitao Ma
Yalan Wang
Haiyan Zhao
Ao-Tian Xu
Yongqiang Wang
Jun Tang
Wen-hai Feng
author_sort Zhitao Ma
title Porcine reproductive and respiratory syndrome virus nonstructural protein 4 induces apoptosis dependent on its 3C-like serine protease activity.
title_short Porcine reproductive and respiratory syndrome virus nonstructural protein 4 induces apoptosis dependent on its 3C-like serine protease activity.
title_full Porcine reproductive and respiratory syndrome virus nonstructural protein 4 induces apoptosis dependent on its 3C-like serine protease activity.
title_fullStr Porcine reproductive and respiratory syndrome virus nonstructural protein 4 induces apoptosis dependent on its 3C-like serine protease activity.
title_full_unstemmed Porcine reproductive and respiratory syndrome virus nonstructural protein 4 induces apoptosis dependent on its 3C-like serine protease activity.
title_sort porcine reproductive and respiratory syndrome virus nonstructural protein 4 induces apoptosis dependent on its 3c-like serine protease activity.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/b7e6535335fe43eaa6baf8b3e6b35c1a
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