TOR3A represses type I interferon production and limits viral clearance during respiratory syncytial virus infection

Type I interferons (IFN-I) are essential for antiviral immunity, and precise regulation of IFN-I production is crucial to balance viral clearance and immunopathology. Here, we demonstrate that the interferon-stimulated gene <i>TOR3A</i> negatively regulates type I IFN signalling during respiratory syncytial virus (RSV) infection. <i>TOR3A</i> expression was upregulated in macrophages and RSV-infected patients, and its deficiency enhanced antiviral responses, leading to reduced viral load. Mechanistically, RSV infection induced <i>TOR3A</i> expression through the IFN-STAT1 pathway, which in turn suppressed IFN-I production. Furthermore, TOR3A recruited the E3 ubiquitin ligase STUB1 to mediate K48-linked ubiquitination and proteasomal degradation of RIG-I at lysine 146, thereby promoting RSV immune evasion. Our study identifies TOR3A as a novel suppressor of antiviral immunity and uncovers a mechanism by which RSV exploits host ISGs to dampen IFN-I responses, providing new insights into viral pathogenesis and potential therapeutic strategies.