Full Text:   <1326>

Summary:  <333>

CLC number: S855.3

On-line Access: 2017-04-05

Received: 2016-05-09

Revision Accepted: 2016-06-05

Crosschecked: 2017-03-17

Cited: 1

Clicked: 1966

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Ying-shan Zhou

http://orcid.org/0000-0002-8011-431X

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Journal of Zhejiang University SCIENCE B 2017 Vol.18 No.4 P.316-323

http://doi.org/10.1631/jzus.B1600208


Porcine circovirus type 2 capsid protein induces unfolded protein response with subsequent activation of apoptosis


Author(s):  Ying-shan Zhou, Yuan-xing Gu, Bao-zhu Qi, Yi-kai Zhang, Xiao-liang Li, Wei-huan Fang

Affiliation(s):  College of Animal Science and Technology, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Zhejiang A&F University, Lin’an 311300, China; more

Corresponding email(s):   whfang@zju.edu.cn

Key Words:  Porcine circovirus 2, Capsid protein, Unfolded protein response, Apoptosis


Ying-shan Zhou, Yuan-xing Gu, Bao-zhu Qi, Yi-kai Zhang, Xiao-liang Li, Wei-huan Fang. Porcine circovirus type 2 capsid protein induces unfolded protein response with subsequent activation of apoptosis[J]. Journal of Zhejiang University Science B, 2017, 18(4): 316-323.

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author="Ying-shan Zhou, Yuan-xing Gu, Bao-zhu Qi, Yi-kai Zhang, Xiao-liang Li, Wei-huan Fang",
journal="Journal of Zhejiang University Science B",
volume="18",
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pages="316-323",
year="2017",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1600208"
}

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%T Porcine circovirus type 2 capsid protein induces unfolded protein response with subsequent activation of apoptosis
%A Ying-shan Zhou
%A Yuan-xing Gu
%A Bao-zhu Qi
%A Yi-kai Zhang
%A Xiao-liang Li
%A Wei-huan Fang
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600208

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T1 - Porcine circovirus type 2 capsid protein induces unfolded protein response with subsequent activation of apoptosis
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A1 - Yi-kai Zhang
A1 - Xiao-liang Li
A1 - Wei-huan Fang
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Abstract: 
Porcine circovirus type 2 (PCV2) has recently been reported to elicit the unfolded protein response (UPR) via activation of the PERK/eIF2α (RNA-activated protein kinase-like endoplasmic reticulum (ER) kinase/eukaryotic initiation factor 2α) pathway. This study attempted to examine which viral protein might be involved in inducing UPR and whether this cellular event would lead to apoptosis of the cells expressing the viral protein. By transient expression, we found that both replicase (Rep) and capsid (Cap) proteins of PCV2 could induce ER stress as shown by increased phosphorylation of PERK with subsequent activation of the eIF2α-ATF4 (activating transcription factor 4)-CHOP (CCAAT/enhancer-binding protein homologous protein) axis. Cap expression, but not Rep, significantly reduced anti-apoptotic B-cell lymphoma-2 (Bcl-2) and increased caspase-3 cleavage, possibly due to increased expression of CHOP. Since knockdown of PERK by RNA interference clearly reduced Cap-induced CHOP expression, caspase-3 cleavage, and apoptotic cell death possibly by partially rescuing Bcl-2 expression, we propose that there is connection between Cap-induced UPR and apoptosis via the PERK/eIF2α/ATF4/CHOP/Bcl-2 pathway. This study, together with our earlier studies, provides insight into the mechanisms underlying PCV2 pathogenesis.

猪圆环病毒2型衣壳蛋白通过未折叠蛋白反应诱导凋亡

目的:确定猪圆环病毒2型衣壳蛋白(PCV2)感染引起未折叠蛋白反应的关键病毒蛋白,以及探究PCV2感染中未折叠蛋白反应与凋亡之间的联系。
创新点:本文首次鉴定出PCV2感染引起未折叠蛋白反应的关键病毒蛋白。
方法:构建表达病毒蛋白的真核表达载体,通过瞬时转染PK-15细胞,采用免疫印迹检测未折叠蛋白反应通路的关键分子;利用RNA干扰抑制perk基因的表达来验证激活的通路;通过抑制内质网上游分子PERK并利用免疫印迹和流式细胞术检测凋亡,研究内质网应激与凋亡之间的联系。
结论:PCV2 Rep和Cap蛋白能激活PERK-eIF2α-ATF4-CHOP通路,PERK通路在Cap诱导的细胞凋亡中起重要作用。

关键词:猪圆环病毒2型;衣壳蛋白;未折叠蛋白反应;凋亡

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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