Department of Medicine II, University of Freiburg, Freiburg, Germany.
J Innate Immun. 2009;1(5):446-54. doi: 10.1159/000226136. Epub 2009 Jun 23.
Toll-like receptors (TLRs) are pathogen recognition molecules activating the innate immune system. Cell surface expressed TLRs, such as TLR2 and TLR4, have been shown to play an important role in human host defenses against viruses through sensing of viral structural proteins. In this study, we aimed to elucidate whether TLR2 and TLR4 participate in inducing antiviral immunity against hepatitis C virus (HCV) by sensing viral structural proteins. We studied TLR2 and TLR4 activation by cell culture-derived infectious virions and serum-derived virions in comparison to purified recombinant HCV structural proteins and enveloped virus-like particles. Incubation of TLR2 or TLR4 transfected cell lines with recombinant core protein resulted in activation of TLR2-dependent signaling. In contrast, neither infectious virions nor enveloped HCV-like particles triggered TLR2 and TLR4 signaling. These findings suggest that monomeric HCV core protein but not intact infectious particles are sensed by TLR2. Impairment of interaction between TLR and the core in infectious viral particles may contribute to escape from innate antiviral immune responses.
Toll 样受体（TLRs）是识别病原体并激活先天免疫系统的分子。已经证实，细胞表面表达的 TLR2 和 TLR4 通过识别病毒的结构蛋白，在人体防御病毒中发挥重要作用。本研究旨在阐明 TLR2 和 TLR4 是否通过识别病毒的结构蛋白来参与诱导抗丙型肝炎病毒（HCV）的抗病毒免疫。我们比较了细胞培养衍生的传染性病毒颗粒和血清衍生的病毒颗粒与纯化的重组 HCV 结构蛋白和包膜病毒样颗粒，研究了 TLR2 和 TLR4 的激活情况。用重组核心蛋白孵育 TLR2 或 TLR4 转染的细胞系可激活 TLR2 依赖性信号转导。相反，传染性病毒颗粒或包膜 HCV 样颗粒均不能触发 TLR2 和 TLR4 信号转导。这些发现表明，单体 HCV 核心蛋白而不是完整的传染性颗粒被 TLR2 识别。在传染性病毒颗粒中，TLR 与核心之间相互作用的受损可能有助于逃避先天抗病毒免疫反应。
