期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 67, 期 14, 页码 2491-2506出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-010-0351-5
关键词
Hepatitis C virus; Non-enveloped particles; Endocytosis; ERK(1/2); c-fos; egr-1
资金
- EU [03Edelta297]
- Greek Ministry of Development-GSRT
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.
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