Activation of p38 MAPK pathway by hepatitis C virus E2 in cells transiently expressing DC-SIGN.
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.
Chen
Qiu-Li
QL
Department of Microbiology, CPLA Key Laboratory of Medical Microbiology, Second Military Medical University, 800 Xiang Yin Road, 200433, Shanghai, China.
Zhu
Shi-Ying
SY
Bian
Zhong-Qi
ZQ
Zhao
Lan-Juan
LJ
Cao
Jie
J
Pan
Wei
W
Qi
Zhong-Tian
ZT
D051698:Activating Transcription Factor 2 / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D037181:Lectins, C-Type / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010957:Plasmids / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D051698:Activating Transcription Factor 2; D015815:Cell Adhesion Molecules; D049452:Green Fluorescent Proteins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D014759:Viral Envelope Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C091015:glycoprotein E2, Hepatitis C virus