Cytotoxicity of ORF3 Proteins from a Nonpathogenic and a Pathogenic Porcine Circovirus

被引:25
作者
Chaiyakul, Mark [1 ,2 ]
Hsu, Karolynn [1 ]
Dardari, Rkia [1 ]
Marshall, Frank [1 ,3 ]
Czub, Markus [1 ,2 ]
机构
[1] Univ Calgary, Fac Vet Med, Dept Prod Anim Hlth, Calgary, AB T2N 4N1, Canada
[2] Univ Calgary, Dept Microbiol & Infect Dis, Fac Med, Calgary, AB T2N 4N1, Canada
[3] Marshall Swine Hlth Serv, Camrose, AB, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
MULTISYSTEMIC WASTING SYNDROME; POLY(ADP-RIBOSE) POLYMERASE; CELL-DEATH; INDUCED APOPTOSIS; SYNDROME PMWS; BINDING; PIGS; DISEASE; TYPE-2; DNA;
D O I
10.1128/JVI.01030-10
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Porcine circovirus type 2 (PCV2) infection is associated with significant and serious swine diseases worldwide, while PCV1 appears to be a nonpathogenic virus. Previous studies demonstrated that the ORF3 protein of PCV2 (PCV2ORF3) was involved in PCV2 pathogenesis via its proapoptotic capability (J. Liu, I. Chen, Q. Du, H. Chua, and J. Kwang, J. Virol. 80: 5065-5073, 2006). If PCV2ORF3-induced apoptosis is a determinant of virulence, PCV1ORF3 is hypothesized to lack this ability. The properties of PCV1 and PCV2 ORF3, expressed as fusion proteins to an enhanced green fluorescent protein (eGFP), were characterized with regard to their ability to cause cellular morphological changes, detachment, death, and apoptosis. PCV1ORF3 significantly induced more apoptotic cell death and was toxic to more different cell types than PCV2ORF3 was. PCV1ORF3-associated cell death was caspase dependent. PCV1ORF3 also induced poly(ADP-ribose) polymerase 1 (PARP) cleavage; however, whether PARP was involved in cell death requires further studies. Truncation of PCV1 and elongation of PCV2 ORF3 proteins revealed that the first 104 amino acids contain a domain capable of inducing cell death, whereas the C terminus of PCV1ORF3 contains a domain possibly responsible for enhancing cell death. These results suggest that the pathogenicity of PCV2 for pigs is either not determined or not solely determined by the ORF3 protein.
引用
收藏
页码:11440 / 11447
页数:8
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