Work

TXNIP promotes viral replication by disrupting MAVS-mediated antiviral signaling and serves as a therapeutic target for antiviral therapy

Year: 2025

Type: article

Abstract: Thioredoxin-interacting protein (TXNIP) is a multifunctional regulator involved in oxidative stress, inflammation, and glucose metabolism. In this study, we investigated the role of TXNIP in viral infection and its potential as a therapeutic target. Our findings reveal that HSV-1 infection induces TXNIP upregulation, and elevated TXNIP levels promote viral replication by inhibiting MAVS aggregation. This inhibition disrupts the TBK1/IRF3 signaling pathway, leading to reduced interferon-beta (IFN-β) production and impaired antiviral immunity. Conversely, TXNIP knockout significantly suppresses HSV-1 infection. Furthermore, we utilized Luteolin, a TXNIP degrader previously reported by our group, which restores MAVS aggregation and enhances antiviral responses, demonstrating potent antiviral effects both in vitro and in vivo. Notably, this mechanism was also validated in dengue virus (DENV2) infection, suggesting a broader role for TXNIP in immune regulation. These findings establish TXNIP as a critical modulator of viral infection and highlight TXNIP degraders as promising candidates for antiviral therapy.

Source: Redox Biology

DOI: 10.1016/j.redox.2025.103756