Abstract:
:HCV culture in vitro results in massive cell death, which suggests the presence of HCV-induced cytopathic effects. Therefore, we investigated its mechanisms and viral nucleotide sequences involved in this effect using HCV-JFH1 cell culture and a newly developed HCV plaque assay technique. The plaque assay developed cytopathic plaques, depending on the titer of the inoculum. In the virus-infected cells, the ER stress markers, GRP78 and phosphorylated eIF2-alpha, were overexpressed. Cells in the plaques were strongly positive for an apoptosis marker, annexin V. Isolated virus subclones from individual plaque showed greater replication efficiency and cytopathogenicity than the parental virus. The plaque-purified virus had 9 amino acid substitutions, of which 5 were clustered in the C terminal of the NS5B region. Taken together, the cytopathic effect of HCV infection involves ER-stress-induced apoptotic cell death. Certain HCV genomic structures may determine the viral replication capacity and cytopathogenicity.
journal_name
Virologyjournal_title
Virologyauthors
Sekine-Osajima Y,Sakamoto N,Mishima K,Nakagawa M,Itsui Y,Tasaka M,Nishimura-Sakurai Y,Chen CH,Kanai T,Tsuchiya K,Wakita T,Enomoto N,Watanabe Mdoi
10.1016/j.virol.2007.09.019subject
Has Abstractpub_date
2008-02-05 00:00:00pages
71-85issue
1eissn
0042-6822issn
1096-0341pii
S0042-6822(07)00597-1journal_volume
371pub_type
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