Department of Pathology and Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, United States of America.
PLoS Negl Trop Dis. 2014 Jun 5;8(6):e2933. doi: 10.1371/journal.pntd.0002933. eCollection 2014 Jun.
The new world arenavirus Junín virus (JUNV) is the causative agent of Argentine hemorrhagic fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that interferon receptor knockout mice succumb to JUNV infection, indicating the critical role of interferon in restricting JUNV infection in mice. Here we report that the pathogenic and vaccine strains of JUNV were highly sensitive to interferon in murine primary cells. Treatment with low concentrations of interferon abrogated viral NP protein expression in murine cells. The replication of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine strain of JUNV displayed impaired growth in primary murine cells. Our data suggested a direct and potent role of host interferon response in restricting JUNV replication in mice. The defect in viral growth for vaccine JUNV might also partially explain its attenuation in mice.
新的世界沙粒病毒胡宁病毒（JUNV）是阿根廷出血热的病原体，这是一种致命的人类传染病。成年实验鼠通常对 JUNV 的外周感染具有抗性。导致鼠类对 JUNV 感染产生抗性的机制在很大程度上是未知的。我们曾报道过，干扰素受体敲除小鼠会因 JUNV 感染而死亡，这表明干扰素在限制 JUNV 在小鼠中的感染方面起着关键作用。在这里，我们报告称，JUNV 的致病性和疫苗株在小鼠原代细胞中对干扰素高度敏感。用低浓度的干扰素处理可消除 NP 蛋白在鼠细胞中的表达。IRF3/IRF7 缺失细胞中 JUNV 的复制增强。此外，JUNV 的疫苗株在原代小鼠细胞中的生长受到损害。我们的数据表明，宿主干扰素反应在限制 JUNV 在小鼠中的复制方面具有直接而强大的作用。疫苗 JUNV 生长缺陷也可能部分解释了其在小鼠中的减毒。
