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J. Virol. doi:10.1128/JVI.00681-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

ORF3 Protein of Porcine Circovirus Type 2 Interacts with Porcine Ubiquitin E3 Ligase Pirh2 and Facilitates p53 Expression in Viral Infection

Animal Health Biotechnology Group, Temasek Life Sciences Laboratory, The National University of Singapore, 1 Research Link, Singapore 117604; Department of Microbiology, Faculty of Medicine, National University of Singapore, Block MD4, 5 Science Drive 2, Singapore 117597

^* To whom correspondence should be addressed. Email: kwang{at}tll.org.sg.

	Abstract

Porcine circovirus type 2 (PCV2) is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome (PMWS). We previously showed that a newly identified protein, ORF3, plays a major role in virus-induced apoptosis and is involved in viral pathogenesis in vitro and in vivo. To characterize the role of the ORF3 protein in modulation of cellular function, a yeast two-hybrid system was used to screen a porcine cDNA library to find its interacting partner. we have isolated and characterized a porcine p53-induced-RING-H2 (pPirh2), an E3 ubiquitin ligase, which specifically interacts with the ORF3 protein of PCV2. This interaction was further confirmed when the ORF3 protein co-immunoprecipated with and co-localized to the pPirh2 in PK15 cells. The ORF3 protein has been found to be interacting with p53 binding domain of the pPirh2 in yeast cells. The expression of the protein results in less pPirh2 expression in PCV2-infected cells. Furthermore, increases in p53 expression were observed in PCV2-infected and ORF3 alone-transfected cells. Phosphorylation of p53 at Ser46, which is related to p53-induced apoptosis, was also time-dependently activated in PCV infected and ORF3 transfected cells. Taken together, our results show that PCV2 ORF3 protein specifically interacts with the pPirh2 and inhibits its stabilization, this may lead to increasing p53 expression, resulting in apoptosis.