Nproof Classical Swine Fever Virus Prevents Type I Interferon-Mediated Priming of Conventional Dendritic Cells for Enhanced Interferon-α Response

2012 ◽  
Vol 32 (5) ◽  
pp. 221-229 ◽  
Author(s):  
Linda Hüsser ◽  
Nicolas Ruggli ◽  
Artur Summerfield
Keyword(s):  
Dendritic Cells ◽  
Classical Swine Fever Virus ◽  
Type I Interferon ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Interferon Α ◽  
Type I ◽  
Mediated Priming

scholarly journals Interaction of classical swine fever virus with dendritic cells

2004 ◽  
Vol 85 (6) ◽  
pp. 1633-1641 ◽  
Author(s):  
C. P. Carrasco ◽  
R. C. Rigden ◽  
I. E. Vincent ◽  
C. Balmelli ◽  
M. Ceppi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Classical Swine Fever Virus ◽  
Specific Antigen ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Immune Reactivity ◽  
Type I ◽  
Antigen Uptake ◽  
Polycytidylic Acid

Functional disruption of dendritic cells (DCs) is an important strategy for viral pathogens to evade host defences. Monocytotropic viruses such as classical swine fever virus (CSFV) could employ such a mechanism, since the virus can suppress immune responses and induce apoptosis without infecting lymphocytes. Here, CSFV was shown to infect and efficiently replicate in monocyte- and in bone marrow-derived DCs. Interestingly, the infected DCs displayed neither modulated MHC nor CD80/86 expression. Stimulation of DCs with IFN-α/TNF-α or polyinosinic–polycytidylic acid (pIC) induced phenotypic maturation with increased MHC and CD80/86 expression, both with mock-treated and infected DCs. In addition, the T cell stimulatory capacity of CSFV-infected DCs was maintained both in a polyclonal T cell stimulation and in specific antigen-presentation assays, requiring antigen uptake and processing. Interestingly, similar to macrophages, CSFV did not induce IFN-α responses in these DCs and even suppressed pIC-induced IFN-α induction. Other cytokines including interleukin (IL)-6, IL-10, IL-12 and TNF-α were not modulated. Taken together, these results demonstrated that CSFV can replicate in DCs and control IFN type I responses, without interfering with the immune reactivity. These results are interesting considering that DC infection with RNA viruses usually results in DC activation.

scholarly journals Npro of classical swine fever virus contributes to pathogenicity in pigs by preventing type I interferon induction at local replication sites

2014 ◽  
Vol 45 (1) ◽  
pp. 47 ◽  
Author(s):  
Tomokazu Tamura ◽  
Naofumi Nagashima ◽  
Nicolas Ruggli ◽  
Artur Summerfield ◽  
Hiroshi Kida ◽  
...  
Keyword(s):  
Classical Swine Fever Virus ◽  
Type I Interferon ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Type I ◽  
Interferon Induction ◽  
Replication Sites

scholarly journals The Structure of Classical Swine Fever Virus Npro: A Novel Cysteine Autoprotease and Zinc-Binding Protein Involved in Subversion of Type I Interferon Induction

2013 ◽  
Vol 9 (10) ◽  
pp. e1003704 ◽  
Author(s):  
Keerthi Gottipati ◽  
Nicolas Ruggli ◽  
Markus Gerber ◽  
Jon-Duri Tratschin ◽  
Matthew Benning ◽  
...  
Keyword(s):  
Classical Swine Fever Virus ◽  
Type I Interferon ◽  
Binding Protein ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Zinc Binding ◽  
Type I ◽  
Interferon Induction

scholarly journals Activation of Dendritic Cells in Tonsils is Associated with CD8 T Cell Responses Following Vaccination with Live Attenuated Classical Swine Fever Virus

2021 ◽  
Vol 22 (16) ◽  
pp. 8795
Author(s):  
Ferran Soldevila ◽  
Jane C. Edwards ◽  
Simon P. Graham ◽  
Helen R. Crooke ◽  
Dirk Werling ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Classical Swine Fever Virus ◽  
T Cell Responses ◽  
Classical Swine Fever ◽  
Cd8 T Cell ◽  
Fever Virus ◽  
Cell Responses ◽  
Strain Vaccine ◽  
Ifn Γ

Classical swine fever (CSF) is a highly contagious disease caused by the classical swine fever virus (CSFV). The live attenuated C-strain vaccine is highly efficacious, initiating protection within several days of delivery. The vaccine strain is detected in the tonsil early after inoculation, yet little is known of the role that tonsillar immune cells might play in initiating protection. Comparing the C-strain vaccine with the pathogenic CSFV Alfort-187 strain, changes in the myeloid cell compartment of the tonsil were observed. CSFV infection led to the emergence of an additional CD163+CD14+ cell population, which showed the highest levels of Alfort-187 and C-strain infection. There was also an increase in both the frequency and activation status (as shown by increased MHC-II expression) of the tonsillar conventional dendritic cells 1 (cDC1) in pigs inoculated with the C-strain. Notably, the activation of cDC1 cells coincided in time with the induction of a local CSFV-specific IFN-γ+ CD8 T cell response in C-strain vaccinated pigs, but not in pigs that received Alfort-187. Moreover, the frequency of CSFV-specific IFN-γ+ CD8 T cells was inversely correlated to the viral load in the tonsils of individual animals. Accordingly, we hypothesise that the activation of cDC1 is key in initiating local CSFV-specific CD8 T cell responses which curtail early virus replication and dissemination.

scholarly journals The N-terminal domain of Npro of classical swine fever virus determines its stability and regulates type I IFN production

2015 ◽  
Vol 96 (7) ◽  
pp. 1746-1756 ◽  
Author(s):  
Junki Mine ◽  
Tomokazu Tamura ◽  
Wasana Pinyochon ◽  
Masatoshi Okamatsu ◽  
Yoshihiro Sakoda ◽  
...  
Keyword(s):  
Classical Swine Fever Virus ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Type I ◽  
Type I Ifn ◽  
Terminal Domain

scholarly journals TNF-Mediated Inhibition of Classical Swine Fever Virus Replication Is IRF1-, NF-κB- and JAK/STAT Signaling-Dependent

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2017
Author(s):  
Matthias Liniger ◽  
Markus Gerber ◽  
Sandra Renzullo ◽  
Obdulio García-Nicolás ◽  
Nicolas Ruggli
Keyword(s):  
Signaling Pathways ◽  
Classical Swine Fever Virus ◽  
Proinflammatory Cytokine ◽  
Classical Swine Fever ◽  
Antiviral Effect ◽  
Fever Virus ◽  
Type I ◽  
Type I Ifn ◽  
Interferon Regulatory Factor 1 ◽  
Necrosis Factor

The sera from pigs infected with virulent classical swine fever virus (CSFV) contain substantial amounts of tumor necrosis factor (TNF), a prototype proinflammatory cytokine with pleiotropic activities. TNF limits the replication of CSFV in cell culture. In order to investigate the signaling involved in the antiviral activity of TNF, we employed small-molecule inhibitors to interfere specifically with JAK/STAT and NF-κB signaling pathways in near-to-primary endothelial PEDSV.15 cells. In addition, we knocked out selected factors of the interferon (IFN) induction and signaling pathways using CRISPR/Cas9. We found that the anti-CSFV effect of TNF was sensitive to JAK/STAT inhibitors, suggesting that TNF induces IFN signaling. Accordingly, we observed that the antiviral effect of TNF was dependent on intact type I IFN signaling as PEDSV.15 cells with the disrupted type I IFN receptor lost their capacity to limit the replication of CSFV after TNF treatment. Consequently, we examined whether TNF activates the type I IFN induction pathway. With genetically modified PEDSV.15 cells deficient in functional interferon regulatory factor 1 or 3 (IRF1 or IRF3), we observed that the anti-CSFV activity exhibited by TNF was dependent on IRF1, whereas IRF3 was dispensable. This was distinct from the lipopolysaccharide (LPS)-driven antiviral effect that relied on both IRF1 and IRF3. In agreement with the requirement of IRF1 to induce TNF- and LPS-mediated antiviral effects, intact IRF1 was also essential for TNF- and LPS-mediated induction of IFN-β mRNA, while the activation of NF-κB was not dependent on IRF1. Nevertheless, NF-κB activation was essential for the TNF-mediated antiviral effect. Finally, we observed that CSFV failed to counteract the TNF-mediated induction of the IFN-β mRNA in PEDSV.15 cells, suggesting that CSFV does not interfere with IRF1-dependent signaling. In summary, we report that the proinflammatory cytokine TNF limits the replication of CSFV in PEDSV.15 cells by specific induction of an IRF1-dependent antiviral type I IFN response.

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