tetano
Editor, Senior Moderator
J Interferon Cytokine Res. 2012 Feb 7. [Epub ahead of print]
N(pro) of Classical Swine Fever Virus Prevents Type I Interferon-Mediated Priming of Conventional Dendritic Cells for Enhanced Interferon-α Response.
H?sser L, Ruggli N, Summerfield A.
Source
Institute of Virology and Immunoprophylaxis , Mittelh?usern, Switzerland .
Abstract
A hallmark of acute classical swine fever is the high interferon (IFN)-α 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-α 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-α 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-β or conditioned medium from CSFV-activated enriched pDC, and expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and IFN-α 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)
oly(C), this was not observed for CSFV. In contrast, the N(pro)(D(136)N) mutant CSFV induced elevated IFN-α 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).
PMID:
22313263
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22313263
N(pro) of Classical Swine Fever Virus Prevents Type I Interferon-Mediated Priming of Conventional Dendritic Cells for Enhanced Interferon-α Response.
H?sser L, Ruggli N, Summerfield A.
Source
Institute of Virology and Immunoprophylaxis , Mittelh?usern, Switzerland .
Abstract
A hallmark of acute classical swine fever is the high interferon (IFN)-α 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-α 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-α 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-β or conditioned medium from CSFV-activated enriched pDC, and expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and IFN-α 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)
oly(C), this was not observed for CSFV. In contrast, the N(pro)(D(136)N) mutant CSFV induced elevated IFN-α 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).PMID:
22313263
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22313263