PRV-Induced mROS–HIF-1α Pathway-Mediated Glycolysis to Promote Replication

Viruses have evolved numerous mechanisms to target key metabolic pathways in the host, thereby reshaping host metabolism to establish a metabolic environment conducive to their replication. We previously observed that pseudorabies virus (PRV) infection upregulates cellular glycolysis, but the mechanism is not clear. Here, our results showed that PRV infection significantly upregulated the mRNA levels of HK2 and MCT4. Upon HIF-1α inhibition, the PRV-induced upregulation of glycolytic genes was reversed. Concurrently, PRV infection promoted the accumulation of intracellular mitochondrial ROS (mROS), whereas mROS inhibition blocked HIF-1α activation. Furthermore, both HIF-1α and mROS inhibition significantly reduced PRV replication. In conclusion, we revealed that PRV activates HIF-1α by inducing mROS accumulation, thereby upregulating key glycolytic genes to promote viral replication. This study provides novel evidence for the metabolic regulatory mechanisms underlying PRV infection and identifies potential targets for PRV and other herpesvirus control.