Abstract：
As a significant infectious disease in livestock, porcine reproductive and respiratory syndrome (PRRS) imposes substantial economic losses on the swine industry. Identification of diagnostic markers and therapeutic targets has been a focal challenge in PPRS prevention and control. By integrating metabolomic and lipidomic serum analyses of clinical pig cohorts through a machine learning approach with in vivo and in vitro infection models, lysophosphatidic acid (LPA) is discovered as a serum metabolic biomarker for PRRS virus (PRRSV) clinical diagnosis. PRRSV promoted LPA synthesis by upregulating the autotaxin expression, which causes innate immunosuppression by dampening the retinoic acid-inducible gene I (RIG-I) and type I interferon responses, leading to enhanced virus replication. Targeting LPA demonstrated protection against virus infection and associated disease outcomes in infected pigs, indicating that LPA is a novel antiviral target against PRRSV. This study lays a foundation for clinical prevention and control of PRRSV infections.
摘要：
作为一种重大的家畜传染病,猪繁殖与呼吸综合征（PRRS）给养猪业带来了巨大的经济损失。诊断标志物和治疗靶标的鉴定一直是PPRS预防和控制中的焦点挑战。通过机器学习方法与体内和体外感染模型整合临床猪队列的代谢组学和脂质组学血清分析，溶血磷脂酸(LPA)是PRRS病毒(PRRSV)临床诊断的血清代谢生物标记物。PRRSV通过上调自分泌运动因子表达促进LPA合成,通过抑制视黄酸诱导基因I（RIG-I）和I型干扰素反应来引起先天免疫抑制，导致病毒复制增强。靶向LPA证明了对感染猪的病毒感染和相关疾病结果的保护作用，表明LPA是针对PRRSV的新型抗病毒靶标。本研究为临床预防和控制PRRSV感染奠定了基础。
