Endocytosis of hepatitis C virus non-enveloped capsid-like particles induces MAPK–ERK1/2 signaling events

• DOI: 10.1007/s00018-010-0351-5
• Publication Date: 2010-03-31T10:32:42Z
• Authors: Konstantina Katsarou; Alexandros Α. Lavdas; Panagiota Tsitoura; Elisavet Serti; Panagiotis Markou...; Penelope Mavromara; Urania Georgopoulou
• Keywords: Cell Nucleus; Mitogen-Activated Protein Kinase 1; 0301 basic medicine; Mitogen-Activated Protein Kinase 3; MAP Kinase Signaling System; Genes, fos; Endosomes; Hep G2 Cells; Hepacivirus; Hydrogen-Ion Concentration; Microtubules; Clathrin; Endocytosis; Cell Line; 3. Good health; Enzyme Activation; 03 medical and health sciences; Cell Line, Tumor; Animals; Humans; Lysosomes; Genes, Immediate-Early; Early Growth Response Protein 1

Although HCV is an enveloped virus, naked nucleocapsids have been reported in the serum of infected patients. The HCV core particle serves as a protective capsid shell for the viral genome and recombinant in vitro assembled HCV core particles induce strong specific immunity. We investigated the post-binding mechanism of recombinant core particle uptake and its intracellular fate. In hepatic cells, these particles are internalized, most likely in a clathrin-dependent pathway, reaching early to late endosomes and finally lysosomes. The endocytic acidic milieu is implicated in trafficking process. Using specific phosphoantibodies, signaling pathway inhibitors and chemical agents, ERK(1/2) was found to be activated in a sustained way after endocytosis, followed by downstream immediate early genes (c-fos and egr-1) modulation. We propose that the intriguing properties of cellular internalization of HCV non-enveloped particles can induce specific ERK(1/2)-MAPKs events that could be important in HCV life cycle and pathogenesis of HCV infection.