Center of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Viral Immunol. 2012 Oct;25(5):387-93. doi: 10.1089/vim.2012.0005. Epub 2012 Jul 9.
The innate immune response induced by Hantavirus is responsible for endothelial cell dysfunction and viral pathogenicity. Recent studies demonstrate that TLR4 expression is upregulated and mediates the secretion of several cytokines in Hantaan virus (HTNV)-infected endothelial cells. To examine viral interactions with host endothelial cells and characterize the innate antiviral responses associated with Toll-like receptors, we selected TLR4 as the target molecule to investigate anti-hantavirus immunity. TLR4 mRNA-silenced EVC-304 (EVC-304 TLR4-) cells and EVC-304 cells were used to investigate signaling molecules downstream of TLR4. The expression of the adaptor protein TRIF was higher in HTNV-infected EVC-304 cells than in EVC-304 TLR4- cells. However, there was no apparent difference in the expression of MyD88 in either cell line. The transcription factors for NF-κB and IRF-3 were translocated from the cytoplasm into the nucleus in HTNV-infected EVC-304 cells, but not in HTNV-infected EVC-304 TLR4- cells. Our results demonstrate that TLR4 may play an important role in the antiviral immunity of the host against HTNV infection through an MyD88-independent signaling pathway.
汉坦病毒诱导的固有免疫反应是导致血管内皮细胞功能障碍和病毒致病性的原因。最近的研究表明，TLR4 的表达上调，并介导汉坦病毒（HTNV）感染的血管内皮细胞中几种细胞因子的分泌。为了研究病毒与宿主内皮细胞的相互作用，并阐明与 Toll 样受体相关的固有抗病毒反应，我们选择 TLR4 作为靶分子来研究抗汉坦病毒免疫。我们使用 TLR4 mRNA 沉默的 EVC-304（EVC-304 TLR4-）细胞和 EVC-304 细胞来研究 TLR4 下游的信号分子。与 EVC-304 TLR4-细胞相比，在 HTNV 感染的 EVC-304 细胞中，衔接蛋白 TRIF 的表达更高。然而，在这两种细胞系中，MyD88 的表达均没有明显差异。NF-κB 和 IRF-3 的转录因子从细胞质易位到细胞核中，这发生在 HTNV 感染的 EVC-304 细胞中，但不会发生在 HTNV 感染的 EVC-304 TLR4-细胞中。我们的结果表明，TLR4 可能通过一种非 MyD88 依赖的信号通路在宿主对 HTNV 感染的抗病毒免疫中发挥重要作用。
