Premium
Silencing of natural interferon producing cell activation by porcine circovirus type 2 DNA
Author(s) -
Vincent Isabelle E.,
Balmelli Carole,
Meehan Brian,
Allan Gordon,
Summerfield Artur,
McCullough Kenneth C.
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02476.x
Subject(s) - porcine circovirus , gene silencing , interferon , virology , biology , dna , genetics , virus , gene
Summary 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.