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Phenotypic and functional alterations of primary human PBMCs induced by HCV non-enveloped capsid-like particles uptake

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Abstract

Hepatitis C virus non-enveloped particles circulate in the serum of HCV-infected patients and are believed to be involved in viral persistence. It was previously demonstrated that recombinant HCVne particles can efficiently enter T cells. In this study we investigated the effect of this entry on the phenotype and function of PBMCs, focused on the CD4+ and CD8+ T-cells. We have generated recombinant HCVne in the absence of other viral proteins. PBMCs from healthy donors were sampled after incubation either with HCVne or the control at different time points. Levels of expression of CD107a, CD25, CTLA-4, and T regulatory cells were estimated and cytokine expression and secretion were also monitored. Peripheral T cells expressed elevated CD127. The intracellular expression of the inhibitory marker CTLA-4 (CD152) increased significantly on peripheral T cells at late hours post-treatment, compared to the respective non-treated group. Despite the fact that there was an initial immune response due to HCVne uptake, T cells were driven to a partial exhausted phenotype. A significant induction of CD4+CD25+hiCD127-regulatory T cells at late hours was observed. Consistently, Foxp3+CD4+ T cells were also increased. In parallel, a significant transcriptional activation and increased secretion of IL-2, IL-10, and IFN-γ, was recorded. Moreover, mRNA transcription of TGF-β was considerably elevated. HCVne particles have the potential to shape the immune response by modifying specific phenotypic and functional markers mainly on CD4+ T cells and driving them to partial exhaustion as well as to Treg expansion.

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Acknowledgments

We thank Dr. P. Foka and Dr. J. M. Werner for useful discussions and M. Georgiou and S. Spiridakis for technical support. This work was supported by the Hellenic Society for the Study of the Liver (ΕΕΜΗ) and Ministry of Education and Religious Affairs, Culture and Sports (Research Program KRIPIS, ESPA 2007–2013).

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Authors and Affiliations

  1. Department of Internal Medicine, Medical School of Athens, Hippokration Hospital, Athens, Greece

    Polyxeni P. Doumba, Maria Boutsikou & John Koskinas

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

    Polyxeni P. Doumba & Manousos M. Konstadoulakis

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

    Elisavet Serti & Urania Georgopoulou

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  1. Polyxeni P. Doumba
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  2. Elisavet Serti
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  4. Manousos M. Konstadoulakis
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  5. Urania Georgopoulou
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  6. John Koskinas
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Correspondence to Urania Georgopoulou or John Koskinas.

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Doumba, P.P., Serti, E., Boutsikou, M. et al. Phenotypic and functional alterations of primary human PBMCs induced by HCV non-enveloped capsid-like particles uptake. Cell. Mol. Life Sci. 70, 3463–3474 (2013). https://doi.org/10.1007/s00018-013-1344-y

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