Present address: INSERM U271, Viral Hepatitis and Associated Pathologies, Lyon, France; †RMIT University, Melbourne, Victoria 3038, Australia.
Silencing of natural interferon producing cell activation by porcine circovirus type 2 DNA
Article first published online: 16 JAN 2007
Volume 120, Issue 1, pages 47–56, January 2007
How to Cite
Vincent, I. E., Balmelli, C., Meehan, B., Allan, G., Summerfield, A. and McCullough, K. C. (2007), Silencing of natural interferon producing cell activation by porcine circovirus type 2 DNA. Immunology, 120: 47–56. doi: 10.1111/j.1365-2567.2006.02476.x
- Issue published online: 16 JAN 2007
- Article first published online: 16 JAN 2007
- Received 19 May 2006; revised 23 August 2006; accepted 23 August 2006.
- natural interferon producing cells;
- porcine circovirus type 2;
- toll-like receptors
Porcine circovirus type 2 (PCV2) infection of natural interferon producing cells (NIPCs) impairs the induction of interferon (IFN)-α and tumour necrosis factor (TNF)-α 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-α, TNF-α, 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.