PDF(Pubmed)
Abstract：
Mammalian arenaviruses are rodent-borne zoonotic viruses, some of which can cause fatal hemorrhagic diseases in humans. The first discovered arenavirus, lymphocytic choriomeningitis virus (LCMV), has a worldwide distribution and can be fatal for transplant recipients. However, no FDA-approved drugs or vaccines are currently available. In this study, using a quantitative proteomic analysis, we identified a variety of host factors that could be needed for LCMV infection, among which we found that protein disulfide isomerase A4 (PDIA4), a downstream factor of endoplasmic reticulum stress (ERS), is important for LCMV infection. Biochemical analysis revealed that LCMV glycoprotein was the main viral component accounting for PDIA4 upregulation. The inhibition of ATF6-mediated ERS could prevent the upregulation of PDIA4 that was stimulated by LCMV infection. We further found that PDIA4 can affect the LCMV viral RNA synthesis processes and release. In summary, we conclude that PDIA4 could be a new target for antiviral drugs against LCMV.
摘要：
哺乳动物沙粒病毒是啮齿动物传播的人畜共患病毒，其中一些会导致人类致命的出血性疾病。第一个发现的沙粒病毒,淋巴细胞脉络膜脑膜炎病毒（LCMV），在全球范围内分布，对移植接受者来说可能是致命的。然而,目前尚无FDA批准的药物或疫苗。在这项研究中,使用定量蛋白质组学分析，我们确定了LCMV感染可能需要的多种宿主因子，其中我们发现蛋白质二硫键异构酶A4（PDIA4），内质网应激（ERS）的下游因素，对LCMV感染很重要。生化分析表明，LCMV糖蛋白是导致PDIA4上调的主要病毒成分。抑制ATF6介导的ERS可以防止LCMV感染刺激的PDIA4的上调。我们进一步发现PDIA4可以影响LCMV病毒RNA的合成过程和释放。总之,我们的结论是,PDIA4可能成为抗LCMV抗病毒药物的新靶点.
