Proapoptotic and pronecrosis effect of different truncated hepatitis C virus core proteins.
OBJECTIVE
To study the roles of different truncated hepatitis C virus (HCV) core proteins (CORE) in the pathogenesis of HCV persistent infection and hepatocellular carcinoma (HCC) and to assess intracellular localization in transiently transfected cells.


METHODS
Seven truncated GFP (green fluorescent protein)-CORE fusion protein expression plasmids were constructed, which contained HCV CORE sequences derived from tumor tissues (BT) and non-tumor tissues (BNT) from one patient infected with HCV. Amino acid (aa) lengths were BT: 1-172 aa, 1-126 aa, 1-58 aa, 59-126 aa, 127-172 aa; BNT: 1-172 aa and C191: 1-172 aa respectively. Subcellular localization of CORE-GFP was analyzed by con-focal laser scanning microscope. Apoptosis and necrosis were quantified by flow cytometry.


RESULTS
Different truncated CORE-GFP localized mainly in the cytoplasm, but nuclear staining was also observed. HCV CORE could induce apoptosis and necrosis, and different truncated COREs could induce cell apoptosis and necrosis at different levels. Among the same length 1-172 aa of BT, BNT and C191, the cell apoptosis and necrosis percentage of BT is highest, and C191 is the lowest (BT>BNT>C191). To the different fragment COREs of BT, N-terminal of CORE induced apoptosis and necrosis higher, compared with that of C-terminal (1-172 aa>1-126 aa>1-58 aa>127-172 aa>59-126 aa).


CONCLUSIONS
These results suggest HCV CORE could induce apoptosis and necrosis of cells, which might play an important role in the pathogenesis of HCV persistent infection and HCC and the different CORE domains of different HCV quasi-species might have some difference in their pathogenesis.
Yan
Xue-bing
XB
Institute of Infectious Diseases, First Affiliated Hospital, Key Laboratory of Health Ministry,School of Medicine, Zhejiang University, Hangzhou 310003, China. yxb007@hotmail.com
Chen
Zhi
Z
Luo
Dong-hui
DH
Xu
Xiao-yan
XY
Wu
Wei
W
Zhou
Lin-fu
LF
D017209:Apoptosis; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D009336:Necrosis / Q000821:virology*; D017384:Sequence Deletion / Q000235:genetics*; D014758:Viral Core Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus