Porcine circovirus type 2 DNA influences cytoskeleton rearrangements in plasmacytoid and monocyte-derived dendritic cells.
Functional disruption of dendritic cells (DC) is an important strategy for viral pathogens to evade host defences. In this context, porcine circovirus type 2 (PCV2), a single-stranded DNA virus, impairs plasmacytoid DC (pDC) and conventional DC activation by certain viruses or Toll-like receptor (TLR) ligands. This inhibitory capacity is associated with the viral DNA, but the impairment does not affect all signalling cascades; TLR7 ligation by small chemical molecules will still induce interleukin-6 (IL-6) and tumour necrosis factor-α secretion, but not interferon-α or IL-12. In this study, the molecular mechanisms by which silencing occurs were investigated. PP2, a potent inhibitor of the Lyn and Hck kinases, produced a similar profile to the PCV2 DNA interference with cytokine secretion by pDC, efficiently inhibiting cell activation induced through TLR9, but not TLR7, ligation. Confocal microscopy and cytometry analysis strongly suggested that PCV2 DNA impairs actin polymerization and endocytosis in pDC and monocyte-derived DC, respectively. Altogether, this study delineates for the first time particular molecular mechanisms involved in PCV2 interference with DC danger recognition, which may be responsible for the virus-induced immunosuppression observed in infected pigs.
Balmelli
Carole
C
Institute of Virology and Immunoprophylaxis, Sensemattstrasse 293, CH-3147 Mittelhäusern, Switzerland. Carole.Balmelli@acw.admin.ch
Steiner
Esther
E
Moulin
Hervé
H
Peduto
Nadja
N
Herrmann
Brigitte
B
Summerfield
Artur
A
McCullough
Kenneth
K
D000199:Actins / Q000037:antagonists & inhibitors / Q000276:immunology; D000818:Animals; D017925:Circovirus / Q000235:genetics* / Q000276:immunology*; D003599:Cytoskeleton / Q000276:immunology*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D056747:Immunomodulation; D015850:Interleukin-6 / Q000378:metabolism; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000821:virology; D011743:Pyrimidines / Q000494:pharmacology; D013552:Swine; D051217:Toll-Like Receptor 9 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
D000199:Actins; D004279:DNA, Viral; D015850:Interleukin-6; D011743:Pyrimidines; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C412373:AG 1879