Downregulation of A20 Expression Increases the Immune Response and Apoptosis and Reduces Virus Production in Cells Infected by the Human Respiratory Syncytial Virus

Human respiratory syncytial virus (HRSV) causes severe lower respiratory tract infections in infants, the elderly, and immunocompromised adults. Regulation of the immune response against HRSV is crucial to limiting virus replication and immunopathology. The A20/TNFAIP3 protein is a negative regulato...

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Published in:Vaccines (Basel) 2020-02, Vol.8 (1), p.100
Main Authors: Martín-Vicente, María, González-Sanz, Rubén, Cuesta, Isabel, Monzón, Sara, Resino, Salvador, Martínez, Isidoro
Format: Article
Language:English
Subjects:
a20
Apoptosis
Gene expression
Health aspects
Immune response
innate immune response
Observations
Respiratory syncytial virus
Ubiquitin-proteasome system
ubiquitination
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Summary:Human respiratory syncytial virus (HRSV) causes severe lower respiratory tract infections in infants, the elderly, and immunocompromised adults. Regulation of the immune response against HRSV is crucial to limiting virus replication and immunopathology. The A20/TNFAIP3 protein is a negative regulator of nuclear factor kappa B (NF-kB) and interferon regulatory factors 3/7 (IRF3/7), which are key transcription factors involved in the inflammatory/antiviral response of epithelial cells to virus infection. Here, we investigated the impact of A20 downregulation or knockout on HRSV growth and the induction of the immune response in those cells. Cellular infections in which the expression of A20 was silenced by siRNAs or eliminated by gene knockout showed increased inflammatory/antiviral response and reduced virus production. Similar results were obtained when the expression of A20-interacting proteins, such as TAX1BP1 and ABIN1, was silenced. Additionally, downregulation of A20, TAX1BP1, and ABIN1 increased cell apoptosis in HRSV-infected cells. These results show that the downregulation of A20 expression might contribute in the control of HRSV infections by potentiating the early innate immune response and increasing apoptosis in infected cells.
ISSN:2076-393X
2076-393X
DOI:10.3390/vaccines8010100