Investigating the Role of A20 in Respiratory Syncytial Virus Immunopathogenesis in a Balb/C Mouse Model Publisher Pubmed



Tahamtan A ; Yasaghi M ; Samadizadeh S ; Nikoo HR ; Yamchi A ; Salimi V
Source: Immunity, Inflammation and Disease Published:2026

Abstract

Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory tract infections in children and the elderly worldwide. RSV pathogenesis is largely driven by exaggerated host immune responses that result in lung injury. In this study, we examined the role of A20 (TNFAIP3), a key regulator of immune signaling, in RSV infection using a BALB/c mouse model. Methods: Recombinant lentiviruses encoding TNFAIP3 (A20) or A20-specific shRNA were generated and administered to BALB/c mice. Animals received intravenous lentivectors, challenged intranasally with RSV-A2, and sacrificed on Day 5 postinfection. A20 expression, cytokine and chemokine levels, lung pathology, and viral load were assessed using real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and histopathological analysis. Results: RSV infection significantly induced A20 expression in bronchoalveolar (BAL) cells. Lentivector-mediated modulation of A20 expression produced distinct outcomes: A20 downregulation amplified inflammatory responses, increased immune cell infiltration, and elevated pro-inflammatory mediator secretion in BAL fluid, leading to aggravated lung pathology. In contrast, A20 upregulation did not markedly alter immune cell recruitment, cytokine production, or histopathological changes following RSV infection. Conclusion: A20 downregulation exacerbates inflammation and lung injury following RSV infection, highlighting its critical role in immune regulation during the virus infection. Further studies employing targeted molecular delivery systems and human airway organoid models are warranted to evaluate the therapeutic potential of modulating A20 in RSV disease. © 2026 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.