Hantaan virus induces toll-like receptor 4 expression, leading to enhanced production of beta interferon, interleukin-6 and tumor necrosis factor-alpha.
Hantaan virus (HTNV) infects endothelial cells and is associated with increased vascular permeability during hemorrhagic fever with renal syndrome (HFRS). The pattern of increased vascular permeability is mediated by immune response. Therefore, it is necessary to characterize the mechanism of HTNV involvement in the host's innate immune. In this study, the expression of five toll-like receptors (TLRs) was analyzed in Endothelial vein cells (EVC-304) following HTNV infection in vitro. TLR4 showed an altered expression after HTNV infection. HTNV infection significantly increased IFN-beta, IL-6 and TNF-alpha secretion from EVC-304 cells, particularly after lipopolysaccharide stimulation. The increased IFN-beta, IL-6 and TNF-alpha production was mediated by TLR4 induction, since the introduction of the small interfering RNA against TLR4 specifically inhibited the HTNV-induced cytokine production. In conclusion, HTNV infection directly induces TLR4 expression and thereby enhanced production of IFN-beta, IL-6 and TNF-alpha, which may contribute to the host's innate immune response.
Jiang
Hong
H
Center of Diagnosis and Treatment for Infectious Diseases, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Wang
Ping-Zhong
PZ
Zhang
Ye
Y
Xu
Zhe
Z
Sun
Li
L
Wang
Li-Mei
LM
Huang
Chang-Xing
CX
Lian
Jian-Qi
JQ
Jia
Zhan-Sheng
ZS
Li
Zhi-Dong
ZD
Bai
Xue-Fan
XF
D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000821:virology*; D018063:Hantaan virus / Q000235:genetics / Q000378:metabolism*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000378:metabolism* / Q000821:virology; D016899:Interferon-beta / Q000096:biosynthesis* / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000378:metabolism
D015850:Interleukin-6; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta