Cytotoxicity of ORF3 proteins from a nonpathogenic and a pathogenic porcine circovirus.
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.
Chaiyakul
Mark
M
Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
Hsu
Karolynn
K
Dardari
Rkia
R
Marshall
Frank
F
Czub
Markus
M
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D048430:Cell Shape; D018173:Circoviridae Infections / Q000473:pathology / Q000821:virology*; D017925:Circovirus / Q000737:chemistry / Q000472:pathogenicity*; D006801:Humans; D013552:Swine; D013553:Swine Diseases / Q000821:virology; D014764:Viral Proteins / Q000633:toxicity*
D014764:Viral Proteins
Virology. 2009 Jan 20;383(2):338-47
19012942
Zentralbl Bakteriol Orig A. 1974 Feb;226(2):153-67
4151202
Nature. 1982 Jan 7;295(5844):64-6
7057875
Mol Cell Biochem. 1999 Mar;193(1-2):137-48
10331650
Virus Genes. 2008 Jun;36(3):509-20
18343985
Biochim Biophys Acta. 1994 Apr 5;1197(1):63-93
8155692
Int J Biochem Cell Biol. 2004 Feb;36(2):223-34
14643888
J Vet Diagn Invest. 2007 Nov;19(6):591-615
17998548
Cell Biol Int. 2010 Jan 25;34(2):225-33
19947924
J Biol Chem. 1999 Aug 13;274(33):22932-40
10438458
Vet Pathol. 2004 Sep;41(5):471-81
15347819
FEBS Lett. 1999 Jan 8;442(1):117-21
9923616
Nature. 1995 Jul 6;376(6535):37-43
7596430
Can Vet J. 1998 Jan;39(1):44-51
9442952
J Biol Chem. 1990 Oct 15;265(29):17420-3
2145274
Vet Immunol Immunopathol. 2004 Jan;97(1-2):25-37
14700535
J Biol Chem. 1989 May 15;264(14):7944-9
2524476
J Vet Med Sci. 2000 Nov;62(11):1125-31
11129853
J Virol. 2006 May;80(10):5065-73
16641298
Immunology. 1985 Oct;56(2):351-8
3876985
Am J Pathol. 1984 Jun;115(3):426-36
6610362
J Exp Med. 1995 Nov 1;182(5):1545-56
7595224
J Biol Chem. 1990 Mar 25;265(9):4923-8
2138622
Cell. 1995 Jun 2;81(5):801-9
7774019
J Virol. 2005 Jul;79(13):8262-74
15956572
J Gen Virol. 1998 Feb;79 ( Pt 2):381-4
9472624
Virus Res. 2009 Aug;143(2):177-83
19647885
Virology. 2009 Oct 10;393(1):104-11
19709712
Apoptosis. 2005 Jan;10(1):75-90
15711924
Cell Death Differ. 2009 Jan;16(1):3-11
18846107
J Vet Diagn Invest. 2008 May;20(3):274-82
18460612
Xenotransplantation. 2004 May;11(3):284-94
15099209
Virus Res. 2010 Jan;147(1):60-6
19852989
J Gen Virol. 2004 Oct;85(Pt 10):2837-2844
15448345
BMC Vet Res. 2005 Oct 31;1:7
16259631