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Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Interferon+Cytokine+Res 2012 ; 32 (5): 221-9 Nephropedia Template TP
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N(pro) of classical swine fever virus prevents type I interferon-mediated priming of conventional dendritic cells for enhanced interferon-alpha response #MMPMID22313263
Husser L; Ruggli N; Summerfield A
J Interferon Cytokine Res 2012[May]; 32 (5): 221-9 PMID22313263show ga
A hallmark of acute classical swine fever is the high interferon (IFN)-alpha levels found in the serum early after infection, followed by an inflammatory cytokine storm. Plasmacytoid dendritic cells (pDCs) represent the only known cell type that produces IFN-alpha upon classical swine fever virus (CSFV) infection in vitro. In primary target cells of the virus the viral protein N(pro) inhibits the induction of type I IFN via the degradation of IRF3. We hypothesized that the early systemic pDC-derived IFN-alpha response sensitizes immune cells for enhanced responsiveness and augment cytokine responses after CSFV infection through the upregulation of IRF7. Therefore, bone marrow-derived granulocyte macrophage-colony stimulating factor (GM-CSF)-induced DCs, were pretreated with IFN-beta or conditioned medium from CSFV-activated enriched pDC, and expression of the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6, and IFN-alpha was assessed after infection with wild-type CSFV and with an N(pro) mutant [N(pro)(D(136)N)] unable to interact with IRF3 and IRF7. While type I IFN treatment sensitized the DCs for enhanced IFN and cytokine responses after stimulation with influenza virus, lipopolysaccharide or poly(I):poly(C), this was not observed for CSFV. In contrast, the N(pro)(D(136)N) mutant CSFV induced elevated IFN-alpha responses in type I IFN-pretreated GM-CSF DCs. These results indicate that CSFV has evolved to prevent type I IFN sensitization in infected cells through the action of the N(pro).