Porcine circovirus type 2 (PCV2) infection of natural interferon producing
cells (NIPCs) impairs the induction of interferon (IFN)-a and
tumour necrosis factor (TNF)-a by cytosine-phosphorothioate-guanine
(CpG) oligodeoxynucleotides (ODNs), thereby preventing both their autocrine
maturation and the paracrine maturation of myeloid dendritic cells
(DCs). The present study shows that the PCV2-mediated inhibition of
NIPCs was mediated by viral DNA, although it was independent of virus
replication. The inhibitory effect of PCV2 DNA was more diversified than
if it had simply targeted CpG-ODN-induced cytokines (IFN-a, TNF-a,
interleukin-6, IL-12). A broad spectrum inhibition was noted, affecting
responses induced by toll-like receptor (TLR)-7 and TLR9 agonists, as
well as viruses including pseudorabies virus, transmissible gastroenteritis
virus and classical swine fever virus. From these results, it would appear
that PCV2 DNA can induce a dominant negative signal influencing independent
pattern recognition receptor-induced activation cascades. Despite
a concomitant internalization of PCV2 DNA and CpG-ODNs, no colocalization
was observed, indicating that PCV2 DNA and CPG-ODNs may not
target the same receptor. This study describes a novel modulation of the
innate immune response, which would render the host more susceptible
to secondary or concomitant microbial infections.