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Activation of p38 MAPK Pathway by Hepatitis C Virus E2 in Cells Transiently Expressing DC-SIGN

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Abstract

Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is a cellular receptor for hepatitis C virus for the binding of viral envelope glycoprotein E2. Interaction of DC-SIGN with the E2 may evoke cellular signal transduction implicated in viral pathogenesis. We developed a cell model with DC-SIGN transient transfection to study p38 mitogen-activated protein kinase (MAPK) signaling pathway in response to the E2 treatment. HEK293T and HeLa were DC-SIGN-deficient cell lines. DC-SIGN was detectable at the surface of HEK293T and HeLa transfected with DC-SIGN, and the levels of DC-SIGN were high in transfected-HEK293T as compared with HeLa. The transfected-HEK293T displayed ability for the E2 binding. In the transfected-HEK293T, level of p38 MAPK phosphorylation was increased upon the E2 treatment and reduced following blockage of DC-SIGN with an antibody against DC-SIGN. Phosphorylation of downstream transcription factor activating transcription factor (ATF)-2 was also up-regulated by the E2 via DC-SIGN. Similar results were obtained with NIH3T3 cells stably expressing DC-SIGN and Huh7 cells. Our results indicate that DC-SIGN transient expression in HEK293T is a useful cell model for investigating p38 MAPK pathway triggered by the E2, which may provide information for understanding cellular receptors-mediated signaling events and the viral pathogenesis.

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Acknowledgments

We thank Drs. S. Pohlmann, F. Baribaud, F. Kirchhoff, R. W. Doms, and D. Thomas (the AIDS Research and Reference Reagent Program, National Institutes of Health) for providing pcDNA3-DC-SIGN plasmid; Drs. T. D. Martin and V. N. KewalRamani for providing NIH3T3/DC-SIGN cells; and Chiron Corporation (Emeryville, USA) for providing HCV E2 protein. This work was supported by grants from the Natural Science Foundation of China 30500021, 30771928 (to L.J.Z.), and 30670089, 30921006 (to Z.T.Q.).

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Authors and Affiliations

  1. Department of Microbiology, CPLA Key Laboratory of Medical Microbiology, Second Military Medical University, 800 Xiang Yin Road, 200433, Shanghai, China

    Qiu-Li Chen, Shi-Ying Zhu, Lan-Juan Zhao, Jie Cao, Wei Pan & Zhong-Tian Qi

  2. Center for Infectious Diseases, CPLA Kunming General Hospital, 650032, Kunming, China

    Zhong-Qi Bian

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  1. Qiu-Li Chen
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Correspondence to Zhong-Tian Qi.

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Qiu-Li Chen, Shi-Ying Zhu—contributed equally to this work.

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Chen, QL., Zhu, SY., Bian, ZQ. et al. Activation of p38 MAPK Pathway by Hepatitis C Virus E2 in Cells Transiently Expressing DC-SIGN. Cell Biochem Biophys 56, 49–58 (2010). https://doi.org/10.1007/s12013-009-9069-0

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