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Journal of Virology, May 2007, p. 4919-4927, Vol. 81, No. 10
0022-538X/07/$08.00+0     doi:10.1128/JVI.02797-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Structure-Dependent Modulation of Alpha Interferon Production by Porcine Circovirus 2 Oligodeoxyribonucleotide and CpG DNAs in Porcine Peripheral Blood Mononuclear Cells{triangledown}

Frida Hasslung Wikström,1* Brian M. Meehan,2,{dagger} Mikael Berg,1,{ddagger} Sirje Timmusk,1 Josefine Elving,1 Lisbeth Fuxler,1 Mattias Magnusson,1,§ Gordon M. Allan,3 Francis McNeilly,3 and Caroline Fossum1

Department of Molecular Bioscience, Section for Veterinary Immunology and Virology, Swedish University of Agricultural Sciences, SE-751 23 Uppsala, Sweden,1 Department of Veterinary Science, Queen's University Belfast,2 Virology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Stormont, Belfast BT4 3SD, United Kingdom3

Received 19 December 2006/ Accepted 16 February 2007

DNA sequences containing CpG motifs are recognized as immunomodulators in several species. Phosphodiester oligodeoxyribonucleotides (ODNs) representing sequences from the genome of porcine circovirus type 2 (PCV2) have been identified as potent inducers (ODN PCV2/5) or inhibitors (ODN PCV2/1) of alpha interferon (IFN-{alpha}) production by porcine peripheral blood mononuclear cells (poPBMCs) in vitro. In this study, the IFN-{alpha}-inducing or -inhibitory activities of specific phosphodiester ODNs were demonstrated to be dependent on their ability to form secondary structures. When a poly(G) sequence was added to a stimulatory self-complementary ODN, high levels of IFN-{alpha} were elicited, and the induction was not dependent on pretreatment with the transfecting agent Lipofectin. In addition, the IFN-{alpha}-inducing ODN required the presence of an intact CpG dinucleotide, whereas the inhibitory activity of ODN PCV2/1 was not affected by methylation or removal of the central CpG dinucleotide. Of particular significance, the IFN-{alpha} inhibition elicited by ODN PCV2/1 was only effective against induction stimulated by DNA control inducers and not RNA control inducers, indicating activity directed to TLR9 signaling. The PCV2 genome as a whole was demonstrated to induce IFN-{alpha} in cultures of poPBMCs, and the presence of immune modulatory sequences within the genome of PCV2 may, therefore, have implications with regard to the immune evasion mechanisms utilized by PCV2.

* Corresponding author. Mailing address: BVF Imm (V), BMC P.O. Box 588, SE-751 23 Uppsala, Sweden. Phone: 46 18 471 4573. Fax: 46 18 471 4382. E-mail: frida.wikstrom{at}bvf.slu.se

{triangledown} Published ahead of print on 28 February 2007.

{dagger} Present address: Department of Biotechnology and Environmental Biology, RMIT University, Melbourne, Victoria 3083, Australia.

{ddagger} Present address: Department of Biomedical Sciences and Veterinary Public Health, Section of Parasitology and Virology, Box 7036, SE-750 07, Uppsala, Sweden.

§ Present address: Department of Rheumatology and Inflammation Research, Göteborg University, Guldhedsgatan 10, SE-413 46 Göteborg, Sweden.

Journal of Virology, May 2007, p. 4919-4927, Vol. 81, No. 10
0022-538X/07/$08.00+0     doi:10.1128/JVI.02797-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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