Porcine Reproductive and Respiratory Syndrome Virus nsp1β Stabilizes HIF-1α to Enhance Viral Replication
Yu Pang, Yanrong Zhou, Yuchen Wang, Zheng Sun, Jiao Liu, Chenyu Li, Shaobo Xiao, Liurong Fang
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) has devastated the swine industry worldwide for over 30 years and shows no signs of slowing down. In this study, we found that PRRSV infection elevated hypoxia-inducible factor 1α (HIF-1α) expression. In addition, overexpressed HIF-1α contributed to PRRSV replication, whereas knockdown of HIF-1α reduced PRRSV growth. The PRRSV-encoded nonstructural protein 1β (nsp1β) exerted a stabilizing effect on HIF-1α through its nuclease protease and papain-like cysteine protease enzymatic domains. PRRSV nsp1β also interacted with von Hippel-Lindau tumor suppressor (pVHL) and HIF-1α, whereby nsp1β impaired the interaction between HIF-1α and pVHL. This work deepens our understanding of the molecular mechanisms involved in PRRSV infection and provides new insights for the development of HIF-1α-based anti-PRRSV therapies.