Endocytosis of hepatitis C virus non-enveloped capsid-like particles induces MAPK-ERK1/2 signaling events.
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.
Katsarou
Konstantina
K
Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.
Lavdas
Alexandros Alpha
AA
Tsitoura
Panagiota
P
Serti
Elisavet
E
Markoulatos
Panagiotis
P
Mavromara
Penelope
P
Georgopoulou
Urania
U
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus; D002966:Clathrin / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics; D004705:Endocytosis; D011992:Endosomes / Q000821:virology; D004789:Enzyme Activation; D017781:Genes, Immediate-Early; D016762:Genes, fos; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000821:virology; D020935:MAP Kinase Signaling System; D008870:Microtubules / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D015533:Transcriptional Activation; D014771:Virion / Q000378:metabolism*
D002966:Clathrin; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3