Porcine circovirus type 2 (PCV2) viral components immunomodulate recall antigen responses Tuija Kekarainen a,1, * , Maria Montoya a,1 , Javier Dominguez c , Enric Mateu a,b , Joaquim Segale ´s a,b a Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Auto `noma de Barcelona, 08193 Bellaterra, Barcelona, Spain b Departament de Sanitat i d’Anatomia Animals, Universitat Auto `noma de Barcelona, 08193 Bellaterra, Barcelona, Spain c Departamento de Biotecnologı ´a, INIA, Ctra de la Corun ˜a, Km 7.5, 28040 Madrid, Spain Received 21 August 2007; received in revised form 19 November 2007; accepted 17 January 2008 Abstract Porcine circovirus type 2 (PCV2) is a single-stranded circular DNA virus infecting domestic pigs worldwide. Interaction of this virus with the immune system apparently modulates the immune response of the host. In the present study, the implication of different components of PCV2 in the modulation of the immune response of the host were investigated by using PCV2 viral-like particles (VLPs) and 16 novel oligodeoxyribonucleotides containing CpG motifs (CpG-ODNs) based on the PCV2 genomic sequence. The role of these viral components was studied by evaluating the cytokine profiles (IFN-a, IFN-g, IL-10, IL-2 and IL-12) on porcine peripheral mononuclear cell (PBMC) and bone marrow-derived dendritic cell (BMDC) cultures. Also, the effect of PCV2 and its elements were examined in recall antigen (pseudorabies virus, PRV) responses. While PCV2 was a potent inducer of IL-10 by PBMCs, such effect was not observed using CpG-ODNs or VLPs. However, IFN-g and IL-2 production by recall antigen was repressed in presence of PCV2 and most of the studied CpG-ODNs. VLPs did not have such repressive effect. In BMDC cultures, PCV2 and most of CpG-ODNs were able to inhibit IFN-a secretion induced by PRV. Interestingly, CpG-ODNs with inhibitory effect were located within the PCV2 Rep gene. Additionally, PCV2 virus was a very strong IL-12 inducer in BMDC cultures. Whereas, IFN-a modulation on BMDC after PCV2 VLP treatment was neglectable, PCV2 VLPs were potent IL-12 inducers. Our data shows that PCV2 viral elements can distinctly regulate cytokine production depending on the cell population studied. Thus, the final immune response upon PCV2 infection seems to depend on the fine balance between the regulatory elements present in viral DNA and structural protein within the host immune system. # 2008 Elsevier B.V. All rights reserved. Keywords: Porcine circovirus type 2 (PCV2); Postweaning multisystemic wasting syndrome (PMWS); Virus-like particles (VLPs); Immune modulation; CpG oligodeoxyribonucleotides (CpG-ODNs); Recall antigen responses 1. Introduction Porcine circovirus type 2 (PCV2) is a single-stranded circular DNA virus infecting domestic pigs worldwide. The clinical course of PCV2 infection range from subclinical to a number of PCV2 associated syndromes, collectively named porcine circovirus diseases (PCVDs); postweaning multisystemic wasting syn- drome (PMWS) is the most economically important PCVD (Segale ´s et al., 2005). PMWS affected pigs suffer a deep alteration of the immune system, including a depletion of T and B www.elsevier.com/locate/vetimm Available online at www.sciencedirect.com Veterinary Immunology and Immunopathology 124 (2008) 41–49 * Corresponding author. Tel.: +34 935814620; fax: +34 935814490. E-mail address: Tuija.Kekarainen@cresa.uab.es (T. Kekarainen). 1 Equally contributing authors. 0165-2427/$ – see front matter # 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.vetimm.2008.01.031