Transition of pseudorabies virus from latency to reactivation state selectively triggered by pathogenic bacteria

Pseudorabies virus (PRV) causes severe morbidity and mortality in pigs and must be eradicated from pig populations. The increasing PRV infections in humans—resulting in severe encephalitis, neurological sequelae, and death since 2017 in China—have also posed a public health risk. PRV can establish latency in pigs, potentially leading to disease outbreaks upon reactivation. However, little is known about the PRV reactivation process, particularly in cases with other pathogens coinfection. We found that extraintestinal pathogenic Escherichia coli and Streptococcus suis , common zoonotic bacteria found in pigs, can trigger PRV reactivation, and bacteria up-regulated CXCL1 to enhance STAT3 phosphorylation and nuclear translocation, which triggers PRV reactivation by regulating the transcription of early viral genes. Effective booster immunization significantly reduced PRV reactivation among pigs. Our work highlights the risk of bacterial coinfections on PRV reactivation, emphasizing the importance of adequate immunization for controlling PRV within pigs and reducing zoonotic transmission.