Key result
PCV2 DNA broadly inhibits natural interferon-producing cells and blunts TLR7 and TLR9 agonist responses.
Why the study?
PCV2 infection impairs interferon and cytokine induction in natural interferon producing cells, but the mechanism of this inhibition was unclear.
PCV2 DNA induces a dominant negative signal that modulates the innate immune response, potentially rendering the host more susceptible to secondary infections.
Hypothesis-generating for viral immune evasion; leaves open relevance to human DC maturation and antiviral responses.
Porcine circovirus type 2 (PCV2) infection of natural interferon producing cells (NIPCs) impairs the induction of interferon (IFN)-alpha and tumour necrosis factor (TNF)-alpha 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-alpha, TNF-alpha, 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.
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Vincent et al. (2006) studied Porcine circovirus type 2 (PCV2) infection. PCV2 DNA was evaluated on Inhibition of natural interferon producing cells (NIPCs). PCV2 DNA mediated a broad-spectrum inhibition of natural interferon producing cells, affecting responses induced by TLR7 and TLR9 agonists as well as various viruses.
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