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Modulation of IL-2 expression after uptake of hepatitis C virus non-enveloped capsid-like particles: the role of p38 kinase

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Abstract

Hepatitis C virus (HCV) has been shown to actively replicate in cells of the immune system, altering both their function and cytokine expression. Naked nucleocapsids have been reported in the serum of infected patients. We investigated interference of recombinant non-enveloped capsid-like particles with signaling pathways in T cells. HCV non-enveloped particles (HCVne) internalization was verified in Jurkat and Hut 78 T cells, as well as primary human peripheral blood and intrahepatic mononuclear cells. HCVne uptake leads to activation of the MAPKs-p38 signaling pathway. Using specific phosphoantibodies, signaling pathways inhibitors, and chemical agents, it was demonstrated that p38 activation in T cells correlated with IL-2 transcriptional activation and was accompanied by a parallel increase of IL-2 cytokine secretion. c-fos and egr-1, two transcription factors, essential for IL-2 promoter activity, were also found to be elevated. We propose that HCVne uptake by T lymphocytes results in increased MAPKs-p38 activity and IL-2 expression, thus altering the host immune response.

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Acknowledgments

This work was supported by PENED 03EΔ297 and co-financed by the EU-European Social Fund (75%) and the Greek Ministry of Development-GSRT (25%).

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  1. Panagiota Tsitoura

    Present address: Insect Molecular Genetics and Biotechnology Group, Institute of Biology, NCSR Demokritos, Athens, Greece

Authors and Affiliations

  1. Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece

    Elisavet Serti, Konstantina Katsarou, Pelagia Foka, Penelope Mavromara & Urania Georgopoulou

  2. Laboratory of Surgical Research, 1st Department of Propaedeutic Surgery, Medical School of Athens, Hippokration Hospital, Athens, Greece

    Polyxeni P. Doumba & Manousos M. Konstandoulakis

  3. 2nd Department of Internal Medicine, Medical School of Athens, Hippokration Hospital, Athens, Greece

    Polyxeni P. Doumba & John Koskinas

  4. Department of Biological Applications and Technology, University of Ioannina, Ioannina, Greece

    George Thyphronitis

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Serti, E., Doumba, P.P., Thyphronitis, G. et al. Modulation of IL-2 expression after uptake of hepatitis C virus non-enveloped capsid-like particles: the role of p38 kinase. Cell. Mol. Life Sci. 68, 505–522 (2011). https://doi.org/10.1007/s00018-010-0466-8

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