Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
J Immunol. 2010 Feb 1;184(3):1168-79. doi: 10.4049/jimmunol.0902750. Epub 2009 Dec 30.
Human metapneumoviruses (HMPVs) are recently identified Paramyxoviridae that contribute to respiratory tract infections in children. No effective treatments or vaccines are available. Successful defense against virus infection relies on early detection by germ line-encoded pattern recognition receptors and activation of cytokine and type I IFN genes. Recently, the RNA helicase retinoic acid-inducible gene I (RIG-I) has been shown to sense HMPV. In this study, we investigated the abilities of two prototype strains of HMPV (A1 [NL\1\00] and B1 [NL\1\99]) to activate RIG-I and induce type I IFNs. Despite the abilities of both HMPV-A1 and HMPV-B1 to infect and replicate in cell lines and primary cells, only the HMPV-A1 strain triggered RIG-I to induce IFNA/B gene transcription. The failure of the HMPV-B1 strain to elicit type I IFN production was dependent on the B1 phosphoprotein, which specifically prevented RIG-I-mediated sensing of HMPV viral 5' triphosphate RNA. In contrast to most cell types, plasmacytoid dendritic cells displayed a unique ability to sense both HMPV-A1 and HMPV-B1 and in this case sensing was via TLR7 rather than RIG-I. Collectively, these data reveal differential mechanisms of sensing for two closely related viruses, which operate in cell type-specific manners.
人偏肺病毒（HMPV）是最近被鉴定出的副黏病毒科病毒，可导致儿童呼吸道感染。目前尚无有效的治疗方法或疫苗。成功抵御病毒感染依赖于由种系编码的模式识别受体的早期检测以及细胞因子和 I 型干扰素基因的激活。最近，RNA 解旋酶视黄酸诱导基因 I（RIG-I）已被证明可感应 HMPV。在这项研究中，我们研究了两种 HMPV 原型株（A1 [NL\1\00]和 B1 [NL\1\99]）激活 RIG-I 和诱导 I 型干扰素的能力。尽管两种 HMPV-A1 和 HMPV-B1 都能够感染和在细胞系和原代细胞中复制，但只有 HMPV-A1 株能够触发 RIG-I 诱导 IFNA/B 基因转录。HMPV-B1 株不能引发 I 型 IFN 产生的原因依赖于 B1 磷蛋白，该蛋白特异性地阻止了 RIG-I 介导的 HMPV 病毒 5'三磷酸 RNA 的感应。与大多数细胞类型不同，浆细胞样树突状细胞显示出一种独特的能力，可以感应到 HMPV-A1 和 HMPV-B1，在这种情况下，感应是通过 TLR7 而不是 RIG-I 进行的。总的来说，这些数据揭示了两种密切相关的病毒的不同感应机制，它们以细胞类型特异性的方式起作用。
