Hepatitis C virus E2 envelope glycoprotein induces an immunoregulatory phenotype in macrophages

ABSTRACT

A comprehensive strategy to control HCV infection needs a vaccine. Our phase I study with recombinant HCV E1/E2 EnvGPs as a candidate vaccine did not induce a strong immune response in volunteers. We analyzed the interactions of HCV EnvGPs with human monocyte derived macrophages as antigen presenting cells. HCV E2 induced immune regulatory cytokine IL-10 and sCD163 protein expression in macrophages from 7 of 9 blood donors tested. Further, HCV E2 enhanced Stat3 and suppressed Stat1 activation, reflecting macrophage polarization towards M2 phenotype. E2 associated macrophage polarization appeared to be dependent of its interaction with CD81 leading EGFR activation. Additionally, E2 suppressed the expression of C3 complement, similar to HCV exposed dendritic cells, implying potential impairment of immune cell priming.

Conclusion: Our results suggest that E2 EnvGP may not be an ideal candidate for HCV vaccine development, and discrete domains within E2 may prove to be more capable of elliciting a protective immune response. This article is protected by copyright. All rights reserved.

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