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Hai-Tao Yu,
Hong Jiang,
Ye Zhang,
Xue-Ping Nan,
Yu Li,
Wei Wang,
Wei Jiang,
Dong-Qiang Yang, Wen-Jing Su,
Jiu-Ping Wang,
Ping-Zhong Wang,
Xue-Fan Bai
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ABSTRACT: 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.
Viral immunology 07/2012; 25(5):387-93. · 1.78 Impact Factor
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Wei Wang,
Ye Zhang,
Yu Li,
Lei Pan,
Lu Bai,
Yan Zhuang,
Chang-Xing Huang,
Jiu-Ping Wang,
Hai-Tao Yu,
Xin Wei,
Wei Jiang,
Ya-Yun Nan,
Dong-Qiang Yang, Wen-Jing Su,
Ping-Zhong Wang,
Xue-Fan Bai
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ABSTRACT: Hantaviruses infect human endothelial cells (ECs) and are known to cause vascular-permeability-based diseases, including hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The αvβ3 integrins, which are highly expressed on the surface of ECs, serve as hantavirus receptors. Specifically, the β3 integrin and vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) form a functional complex and interact with each other. Signaling through this complex causes cytoskeletal reorganization, which is one of the most important mechanisms underlying hyperpermeability. In this study, we show that VEGF dramatically enhances Hantaan virus (HTNV)-directed permeability and increases the reorganization of the cytoskeleton and the disruption of junctional organizations in an EC monolayer at 3 days postinfection. HTNV infection reduced the effect of VEGF on adhesion, migration, and the upregulation of β3 expression, but the infection alone upregulated the expression of β3 and VEGFR2. These results indicate that in addition to its role in blocking β3 integrin activation as reported previously, HTNV blocks the function of the complex of VEGFR2 and β3 integrin, and the dysfunction of the complex may contribute to cytoskeletal reorganization in an HTNV-directed hyperpermeability response to VEGF.
Archives of Virology 03/2012; 157(6):1051-61. · 2.11 Impact Factor
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ABSTRACT: To observe the immunization effect to HBsAg by B7-H1 protein vaccine in transgenic mice, and to explore new methods for the treatment of chronic hepatitis B.
After the joint immunization in HBV transgenic mice with different doses of hepatitis B virus (HBV) vaccine and B7-H1 protein, the anti-B7-H1 antibody titors, Th1 type of cytokines (IFN-γ and IL-2) from the spleen cells of mice, the number of theT cells secreting IFN-γ and the number of the mice lymphocyte proliferation were mesrued by ELISA, ELISPOT and MTT technique respectively, to compare the immune effect of different immune methods and regimen.
The immune plans were completed successfully. The anti-B7-H1 antibody was detected in the fifth week after immunization with B7-H1 vaccine, at the same time no obvious difference of antibodies titors between groups were found. IL-2 and the number of T cells secreting IFN-γ were significantly reduced(P<0.05)in joint immunization group with B7-H1 protein and HBsAg, but no difference in other immune tests, such as IFN-γ, lymphocyte proliferation.
A lower doses of HBsAg can cause the secretion of Th1 type of cytokines and lymphocyte proliferation. B7-H1 protein vaccines have a better immunogetic effect for HBV transgenic mice, but can notupregulate the immune response to HBsAg.
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 02/2012; 28(2):113-6.
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ABSTRACT: Chronic hepatitis B is characterized by an impaired immune response to hepatitis B virus (HBV). Telbivudine treatment has significantly improved the clinical outcome of chronic HBV infection. However, the underlying mechanism behind the antiviral response of patients treated with nucleoside analogs remains unclear. To gather more evidence about the mechanism responsible for the weak immune response, in this study we analyzed the effects on HBV viral load of treatment with the nucleoside analogue telbivudine and the percentage of Tregs, programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, and related cytokine production. Peripheral blood mononuclear cells (PBMCs) and serum of 28 patients with chronic hepatitis B were collected at baseline, and 3 mo and 6 mo after therapy was begun. In parallel with the decline in viral load and serum ALT normalization, we found a decline in circulating CD4(+)CD25(high) Tregs, PD-L1 on CD4(+) T cells, and IL-9 production. The expression of PD-1 on CD4(+) T cells and the production of IFN-γ did not increase during therapy. Our findings suggest that the antiviral effect of the nucleoside analogs may be attributable not only to their direct effect on virus suppression, but also to their immunoregulatory capabilities.
Viral immunology 02/2012; 25(1):21-8. · 1.78 Impact Factor
