Role of p53/NF-κB functional balance in respiratory syncytial virus-induced inflammation response.

Abstract

The interplay between respiratory syncytial virus (RSV) and the p53 pathway has only been reported in a limited number of studies, yet the underlying abrogation mechanisms of p53 activity during the time course of infection, possibly involving viral proteins, remained unclear. Here, we demonstrate that RSV infection impairs global p53 transcriptional activity, notably via its proteasome-dependent degradation at late stages of infection. We also demonstrate that NS1 and NS2 contribute to the abrogation of p53 activity, and used different experimental strategies (e.g. siRNA, small molecules) to underline the antiviral contribution of p53 in the context of RSV infection. Notably, our study highlights a strong RSV-induced disequilibrium of the p53/NF-κB functional balance, which appears to contribute to the up-regulation of the expression of several proinflammatory cytokines and chemokines.

• Authors: Daniela Machado, Andrés Pizzorno, Jonathan Hoffmann, Aurélien Traversier, Hubert Endtz, Bruno Lina, Manuel Rosa-Calatrava, Gláucia Paranhos-Baccala, Olivier Terrier
• Journal: The Journal of general virology (J Gen Virol) Vol. 99 Issue 4 Pg. 489-500 (04 2018) ISSN: 1465-2099 [Electronic] England
• PMID: 29504924 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• NF-kappa B
• Tumor Suppressor Protein p53
• Viral Nonstructural Proteins
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Proteasome Endopeptidase Complex

Topics

• Cytokines (genetics, immunology)
• Humans
• NF-kappa B (genetics, metabolism)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Proteasome Endopeptidase Complex (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Respiratory Syncytial Virus Infections (genetics, immunology, metabolism, virology)
• Respiratory Syncytial Virus, Human (genetics, physiology)
• Signal Transduction
• Tumor Suppressor Protein p53 (genetics, metabolism)
• Viral Nonstructural Proteins (genetics, metabolism)