# NUDT7 Modulates the UBA52-SREBF1 Signaling Axis to Promote PRRSV Replication via Lipid Synthesis

## TL;DR

This study identifies NUDT7 as a host protein that promotes PRRSV replication by modulating lipid synthesis and immune evasion.

## Contribution

The study reveals a novel NUDT7-UBA52-SREBF1 signaling axis that modulates lipid metabolism and immune evasion during PRRSV infection.

## Key findings

- NUDT7 expression is upregulated during PRRSV infection via ETS1 promoter targeting.
- NUDT7 promotes PRRSV replication by enhancing lipid droplet formation and stabilizing SREBF1.
- NUDT7 inhibits type I interferon signaling, aiding viral immune evasion.

## Abstract

Identifying cellular proteins and processes crucial for viral infection is vital for comprehending virus-induced disease mechanisms and developing host-targeted therapies. PRRSV has been shown to take advantage of host metabolic reprogramming and immunosuppression to promote virus production, but the host factors that coordinate these processes have not been fully elucidated. Here, we showed that NUDT7 expression was significantly increased during PRRSV infection by ETS1 targeting its promoter. We also found NUDT7 enhance PRRSV replication by reprograms viral infection-induced intracellular lipid droplets (LDs) synthesis. Mechanistically, NUDT7 interacts with and targets the ubiquitin-ribosomal fusion protein UBA52 for proteasomal degradation. NUDT7 enhances lipid droplet formation and stabilizes the lipogenic transcription factor SREBF1 by blocking UBA52-mediated K11/K27/K48 polyubiquitination. NUDT7-UBA52-SREBF1 axis drives lipid metabolic reprogramming, creating a favorable environment for PRRSV replication. Additionally, NUDT7 inhibits type I interferon signaling and the expression of interferon-stimulated genes, facilitating viral immune evasion. These findings suggest that NUDT7 could be a therapeutic target for combating PRRSV infection, offering a novel perspective and theoretical foundation for developing targeted metabolic-immune antiviral strategies.