Department of Microbiology and Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Virol. 2011 Nov;85(21):11058-68. doi: 10.1128/JVI.05304-11. Epub 2011 Aug 31.
Junín virus is the causative agent for Argentine hemorrhagic fever, and its natural host is the New World rodent Calomys musculinus. The virus is transmitted to humans by aerosolization, and it is believed that many of the clinical symptoms are caused by cytokines produced by sentinel cells of the immune system. Here we used the Junín virus vaccine strain Candid 1 to determine whether mouse cells could be used to study virus entry and antiviral innate immune responses. We show that Candid 1 can infect and propagate in different mouse-derived cell lines through a low-pH-dependent, transferrin receptor 1-independent mechanism, suggesting that there is a second entry receptor. In addition, Candid 1 induced expression of the antiviral cytokines tumor necrosis factor alpha and beta interferon in macrophages, and this induction was independent of viral replication. Using Candid 1, as well as virus-like particles bearing the viral glycoprotein, to infect different primary cells and established macrophage cell lines with deletions in the Toll-like receptor (TLR) pathway, we show that TLR2 is a cellular sensor of both the Parodi and Candid 1 viral glycoproteins. Because Junín virus is highly lethal in humans, the use of an experimentally tractable model system, such as the mouse, could provide a better understanding of the antiviral innate cellular responses to Junín virus and the role of these responses in pathogenesis.
胡宁病毒是阿根廷出血热的病原体，其自然宿主是新世界啮齿动物 Calomys musculinus。该病毒通过气溶胶化传播给人类，人们认为许多临床症状是由免疫系统的哨兵细胞产生的细胞因子引起的。在这里，我们使用胡宁病毒疫苗株 Candid 1 来确定小鼠细胞是否可用于研究病毒进入和抗病毒先天免疫反应。我们表明，Candid 1 可以通过低 pH 值依赖、转铁蛋白受体 1 非依赖的机制感染和在不同的小鼠来源的细胞系中繁殖，这表明存在第二个进入受体。此外，Candid 1 诱导巨噬细胞中抗病毒细胞因子肿瘤坏死因子-α和β干扰素的表达，这种诱导不依赖于病毒复制。使用 Candid 1 以及携带病毒糖蛋白的病毒样颗粒感染具有 Toll 样受体 (TLR) 途径缺失的不同原代细胞和已建立的巨噬细胞系，我们表明 TLR2 是 Parodi 和 Candid 1 病毒糖蛋白的细胞传感器。由于胡宁病毒在人类中具有高度致命性，使用实验上易于处理的模型系统（如小鼠）可以更好地了解抗病毒先天细胞对胡宁病毒的反应以及这些反应在发病机制中的作用。
