Porcine reproductive and respiratory syndrome virus-mediated lactate facilitates virus replication by targeting MAVS

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important causative agents in the pig industry worldwide, causing reproductive failure in sows and respiratory problems in growing pigs. Glucose metabolism is a major pathway for energy production and interacts with many cellular processes, such as innate immunity response. It is unclear whether PRRSV infection can use the glucose metabolic pathway to generate immune escape in favor of viral replication. Here, we found that high glucose promotes PRRSV replication and glycolysis, and inhibits poly(I:C)-induced RLR signaling. Conversely, inhibition of the glycolysis pathway significantly promoted poly(I:C)-induced RLR signaling and inhibited PRRSV replication, suggesting that glycolysis promotes PRRSV replication by inhibiting interferon signaling. Furthermore, PRRSV promotes glycolysis to produce lactate, which acts as a key metabolite to promote viral replication by inhibiting RLR signaling by targeting MAVS. And the glycolytic inhibitors targeting HK2 and LDHA in glycolysis could inhibit PRRSV replication. Taken together, these findings suggested that PRRSV infection promotes glycolysis to produce lactate, which targets MAVS to inhibit RLR signaling and thus promote viral replication. Our findings provide an insight into the pathogenesis of PRRSV and offer a theoretical basis for further development of antiviral therapeutic targets.

Automated summary

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen in the global pig industry, causing reproductive failure and respiratory problems. This study found that high glucose promotes PRRSV replication by inhibiting interferon signaling, while inhibition of the glycolysis pathway suppresses viral replication and enhances immune response. PRRSV also promotes glycolysis to produce lactate, which targets MAVS to inhibit immune signaling and promote viral replication. These findings provide insights into the pathogenesis of PRRSV and offer potential therapeutic targets for antiviral development.