Premium
Hepatitis C virus infection induces endoplasmic reticulum stress and apoptosis in human fetal liver stem cells
Author(s) -
Guo Xuan,
Liu WeiLi,
Yang Dong,
Shen ZhiQiang,
Qiu ZhiGang,
Jin Min,
Li JunWen
Publication year - 2019
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5240
Subject(s) - endoplasmic reticulum , apoptosis , biology , xiap , vacuolization , unfolded protein response , stem cell , microbiology and biotechnology , mitochondrion , hepatitis c virus , programmed cell death , virology , cancer research , caspase , virus , endocrinology , biochemistry
The cellular mechanisms by which hepatitis C virus (HCV) replication might mediate cytopathic effects are controversial and not entirely clear. In this study, we found that blood‐borne HCV (bbHCV) infection could lead to endoplasmic reticulum (ER)‐stress and mitochondria‐related/caspase‐dependent apoptosis at the early stages of infection based on use of the highly efficient bbHCV cell culture model established previously. Sections of bbHCV‐infected human fetal liver stem cells (hFLSCs) revealed convolution and nonlinear ER, cell vacuolization, swelling of mitochondria, and numerous double membrane vesicles (DMVs). The percentage of apoptotic hFLSCs infected by bbHCV reached 29.8% at 16 h postinfection, and the amount of cytochrome c increased remarkably in the cytosolic protein fraction. However, over time, apoptosis was inhibited due to the activation of NF‐κB. The expression of NF‐κB‐p65, Bcl‐xL, XIAP, and c‐FLIPL in hFLSCs was increased significantly 24 h after in infection by bbHCV. The accelerated cell death cycles involving apoptosis, regeneration and repair by bbHCV infection might give rise to the development of cirrhosis, and ultimately to hepatocellular carcinogenesis. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.