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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
First Insight into the Modulation of Noncanonical NF-κB Signaling Components by Poxviruses in Established
Justyna Struzik1, Lidia Szulc-Dąbrowska1, Matylda B Mielcarska1
1Division of Immunology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences-SGGW, Ciszewskiego 8, 02-786 Warsaw, Poland.
Abstract:
Dendritic cells (DCs) and macrophages are the first line of antiviral immunity. Viral pathogens exploit these cell populations for their efficient replication and dissemination via the modulation of intracellular signaling pathways. Disruption of the noncanonical nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling has frequently been observed in lymphoid cells upon infection with oncogenic viruses. However, several nononcogenic viruses have been shown to manipulate the noncanonical NF-κB signaling in different cell types. This study demonstrates the modulating effect of ectromelia virus (ECTV) on the components of the noncanonical NF-κB signaling pathway in established murine cell lines: JAWS II DCs and RAW 264.7 macrophages. ECTV affected the activation of TRAF2, cIAP1, RelB, and p100 upon cell treatment with both canonical and noncanonical NF-κB stimuli and thus impeded DNA binding by RelB and p52. ECTV also inhibited the expression of numerous genes related to the noncanonical NF-κB pathway and RelB-dependent gene expression in the cells treated with canonical and noncanonical NF-κB activators. Thus, our data strongly suggest that ECTV influenced the noncanonical NF-κB signaling components in the in vitro models. These findings provide new insights into the noncanonical NF-κB signaling components and their manipulation by poxviruses in vitro.
Insights
Ectromelia virus (ECTV) disrupts antiviral immunity by interfering with the noncanonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in dendritic cells and macrophages. This viral manipulation impedes immune responses, offering insights into poxvirus infection mechanisms.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Dendritic cells (DCs) and macrophages are crucial for innate antiviral immunity.
- Viral pathogens often manipulate host cell signaling pathways, including NF-κB, for replication.
- The noncanonical NF-κB pathway's role in antiviral immunity and viral manipulation is an area of active research.
Purpose of the Study:
- To investigate the effect of ectromelia virus (ECTV) on the noncanonical NF-κB signaling pathway.
- To determine how ECTV modulates key components of this pathway in immune cells.
- To understand ECTV's strategy for immune evasion through NF-κB pathway disruption.
Main Methods:
- Utilized established murine cell lines: JAWS II dendritic cells and RAW 264.7 macrophages.
- Treated cells with ECTV and assessed the activation of NF-κB pathway components (TRAF2, cIAP1, RelB, p100).
- Analyzed the impact of ECTV on DNA binding activity of RelB and p52 transcription factors.
- Quantified the expression of NF-κB pathway-related and RelB-dependent genes.
Main Results:
- ECTV modulated the activation of TRAF2, cIAP1, RelB, and p100 in response to NF-κB stimuli.
- ECTV impeded the DNA binding of RelB and p52 transcription factors.
- ECTV inhibited the expression of genes regulated by the noncanonical NF-κB pathway and RelB.
- These effects were observed in both canonical and noncanonical NF-κB activation conditions.
Conclusions:
- ECTV significantly influences the noncanonical NF-κB signaling pathway components in vitro.
- ECTV's manipulation of this pathway likely contributes to immune evasion during infection.
- Findings provide novel insights into poxvirus-host interactions and immune signaling disruption.
