Key result
Specific PCV2 oligodeoxyribonucleotides modulate porcine IFN-alpha production depending on secondary structure and intact CpG dinucleotides.
Why the study?
The immunomodulatory effects of phosphodiester oligodeoxyribonucleotides from the PCV2 genome on IFN-alpha production by porcine PBMCs and their structural dependence were unclear.
PCV2 ODNs modulate IFN-alpha production in porcine PBMCs dependent on secondary structure and TLR9 signaling, suggesting potential immune evasion mechanisms by PCV2.
May indicate PCV2 immune evasion in porcine cells; leaves open in vivo validation and translational relevance.
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.
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Wikström et al. (2007) studied this question. Phosphodiester oligodeoxyribonucleotides (ODNs) from PCV2 vs. DNA and RNA control inducers was evaluated on Alpha interferon (IFN-alpha) production. Specific PCV2 oligodeoxyribonucleotides modulated IFN-alpha production in porcine peripheral blood mononuclear cells dependent on their secondary structure and intact CpG dinucleotides.
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