title: Hantaan virus triggers TLR4-dependent innate immune responses.
abstract: 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.
authors: Center of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors: Hai-Tao
authors: HT
authors: Yu
authors: Hong
authors: H
authors: Jiang
authors: Ye
authors: Y
authors: Zhang
authors: Xue-Ping
authors: XP
authors: Nan
authors: Yu
authors: Y
authors: Li
authors: Wei
authors: W
authors: Wang
authors: Wei
authors: W
authors: Jiang
authors: Dong-Qiang
authors: DQ
authors: Yang
authors: Wen-Jing
authors: WJ
authors: Su
authors: Jiu-Ping
authors: JP
authors: Wang
authors: Ping-Zhong
authors: PZ
authors: Wang
authors: Xue-Fan
authors: XF
authors: Bai
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000096:biosynthesis; D002460:Cell Line; D042783:Endothelial Cells / Q000821:virology; D018063:Hantaan virus / Q000276:immunology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D050838:Interferon Regulatory Factor-3; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017472:Receptors, Interleukin-1; C470409:TICAM1 protein, human; C434984:TIRAP protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4