LGALS3BP/90K suppresses porcine reproductive and respiratory syndrome virus replication by enhancing GP3 degradation and stimulating innate immunity.

Porcine reproductive and respiratory syndrome virus (PRRSV) seriously affects the world pig industry, and existing vaccines are not enough to protect against PRRSV efficiently. Identifying host factors that inhibit PRRSV infection may provide potential targets for antiviral therapies. Galectin 3 binding protein (LGALS3BP), also referred to as 90K, is a multifunctional protein that plays significant roles in viral infections, but its role in PRRSV infection is not clearly defined. In this study, we found that 90K expression increased during PRRSV infection. Additionally, 90K inhibits PRRSV replication by restricting both viral RNA synthesis and viral assembly. Further studies showed that 90K can interact with various PRRSV structural proteins, such as GP2, GP3, and GP5. Moreover, 90K targets K217 in GP3 for K48-linked ubiquitination, facilitating GP3 degradation through the proteasomal pathway. Meanwhile, we found that 90K induces the expression of type I interferon (IFN) and inflammatory cytokines by activating NF-κB and IRF3. Overall, our findings suggest that 90K plays a negative role in PRRSV replication by inducing PRRSV-GP3 degradation and activating innate immune responses.