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

## TL;DR

This study shows how the gene TOR3A helps the respiratory syncytial virus avoid the immune system by reducing interferon production.

## Contribution

TOR3A is identified as a new suppressor of antiviral immunity during RSV infection.

## Key findings

- TOR3A limits viral clearance by suppressing type I interferon production.
- RSV induces TOR3A via the IFN-STAT1 pathway to evade immune responses.
- TOR3A promotes RIG-I degradation through ubiquitination, aiding RSV immune evasion.

## Abstract

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 TOR3A negatively regulates type I IFN signalling during respiratory syncytial virus (RSV) infection. TOR3A expression was upregulated in macrophages and RSV-infected patients, and its deficiency enhanced antiviral responses, leading to reduced viral load. Mechanistically, RSV infection induced TOR3A 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.