Structure-dependent modulation of alpha interferon production by porcine circovirus 2 oligodeoxyribonucleotide and CpG DNAs in porcine peripheral blood mononuclear cells.
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.
Wikström
Frida Hasslung
FH
Department of Molecular Bioscience, Section for Veterinary Immunology and Virology, Swedish University of Agricultural Sciences, SE-751 23 Uppsala, Sweden. frida.wikstrom@bvf.slu.se
Meehan
Brian M
BM
Berg
Mikael
M
Timmusk
Sirje
S
Elving
Josefine
J
Fuxler
Lisbeth
L
Magnusson
Mattias
M
Allan
Gordon M
GM
McNeilly
Francis
F
Fossum
Caroline
C
D000818:Animals; D001483:Base Sequence; D017925:Circovirus / Q000235:genetics / Q000276:immunology*; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology*; D015226:Dinucleoside Phosphates / Q000737:chemistry; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013552:Swine; D051217:Toll-Like Receptor 9 / Q000502:physiology
D004279:DNA, Viral; D015226:Dinucleoside Phosphates; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; C408982:CPG-oligonucleotide; C015772:CpG dinucleotide