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Mitochondrial Localization Signal of Porcine Circovirus Type 2 Capsid Protein Plays a Critical Role in Cap-Induced Apoptosis

Porcine circovirus 2 (PCV2), considered one of the most globally important porcine pathogens, causes postweaning multisystemic wasting syndrome (PMWS). This virus is localized in the mitochondria in pigs with PMWS. Here, we identified, for the first time, a mitochondrial localization signal (MLS) in...

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Autores principales: Yu, Wanting, Sun, Yuao, He, Qing, Sun, Chaoying, Dong, Tian, Zhang, Luhua, Zhan, Yang, Wang, Naidong, Yang, Yi, Sun, Yujie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624748/
https://www.ncbi.nlm.nih.gov/pubmed/34822645
http://dx.doi.org/10.3390/vetsci8110272
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author Yu, Wanting
Sun, Yuao
He, Qing
Sun, Chaoying
Dong, Tian
Zhang, Luhua
Zhan, Yang
Wang, Naidong
Yang, Yi
Sun, Yujie
author_facet Yu, Wanting
Sun, Yuao
He, Qing
Sun, Chaoying
Dong, Tian
Zhang, Luhua
Zhan, Yang
Wang, Naidong
Yang, Yi
Sun, Yujie
author_sort Yu, Wanting
collection PubMed
description Porcine circovirus 2 (PCV2), considered one of the most globally important porcine pathogens, causes postweaning multisystemic wasting syndrome (PMWS). This virus is localized in the mitochondria in pigs with PMWS. Here, we identified, for the first time, a mitochondrial localization signal (MLS) in the PCV2 capsid protein (Cap) at the N-terminus. PK-15 cells showed colocalization of the MLS-EGFP fusion protein with mitochondria. Since the PCV2 Cap also contained a nuclear localization signal (NLS) that mediated entry into the nucleus, we inferred that the subcellular localization of the PCV2 Cap is inherently complex and dependent on the viral life cycle. Furthermore, we also determined that deletion of the MLS attenuated Cap-induced apoptosis. More importantly, the MLS was essential for PCV2 replication, as absence of the MLS resulted in failure of virus rescue from cells infected with infectious clone DNA. In conclusion, the MLS of the PCV2 Cap plays critical roles in Cap-induced apoptosis, and MLS deletion of Cap is lethal for virus rescue.
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spelling pubmed-86247482021-11-27 Mitochondrial Localization Signal of Porcine Circovirus Type 2 Capsid Protein Plays a Critical Role in Cap-Induced Apoptosis Yu, Wanting Sun, Yuao He, Qing Sun, Chaoying Dong, Tian Zhang, Luhua Zhan, Yang Wang, Naidong Yang, Yi Sun, Yujie Vet Sci Article Porcine circovirus 2 (PCV2), considered one of the most globally important porcine pathogens, causes postweaning multisystemic wasting syndrome (PMWS). This virus is localized in the mitochondria in pigs with PMWS. Here, we identified, for the first time, a mitochondrial localization signal (MLS) in the PCV2 capsid protein (Cap) at the N-terminus. PK-15 cells showed colocalization of the MLS-EGFP fusion protein with mitochondria. Since the PCV2 Cap also contained a nuclear localization signal (NLS) that mediated entry into the nucleus, we inferred that the subcellular localization of the PCV2 Cap is inherently complex and dependent on the viral life cycle. Furthermore, we also determined that deletion of the MLS attenuated Cap-induced apoptosis. More importantly, the MLS was essential for PCV2 replication, as absence of the MLS resulted in failure of virus rescue from cells infected with infectious clone DNA. In conclusion, the MLS of the PCV2 Cap plays critical roles in Cap-induced apoptosis, and MLS deletion of Cap is lethal for virus rescue. MDPI 2021-11-10 /pmc/articles/PMC8624748/ /pubmed/34822645 http://dx.doi.org/10.3390/vetsci8110272 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yu, Wanting
Sun, Yuao
He, Qing
Sun, Chaoying
Dong, Tian
Zhang, Luhua
Zhan, Yang
Wang, Naidong
Yang, Yi
Sun, Yujie
Mitochondrial Localization Signal of Porcine Circovirus Type 2 Capsid Protein Plays a Critical Role in Cap-Induced Apoptosis
title Mitochondrial Localization Signal of Porcine Circovirus Type 2 Capsid Protein Plays a Critical Role in Cap-Induced Apoptosis
title_full Mitochondrial Localization Signal of Porcine Circovirus Type 2 Capsid Protein Plays a Critical Role in Cap-Induced Apoptosis
title_fullStr Mitochondrial Localization Signal of Porcine Circovirus Type 2 Capsid Protein Plays a Critical Role in Cap-Induced Apoptosis
title_full_unstemmed Mitochondrial Localization Signal of Porcine Circovirus Type 2 Capsid Protein Plays a Critical Role in Cap-Induced Apoptosis
title_short Mitochondrial Localization Signal of Porcine Circovirus Type 2 Capsid Protein Plays a Critical Role in Cap-Induced Apoptosis
title_sort mitochondrial localization signal of porcine circovirus type 2 capsid protein plays a critical role in cap-induced apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624748/
https://www.ncbi.nlm.nih.gov/pubmed/34822645
http://dx.doi.org/10.3390/vetsci8110272
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