Hepatitis C virus core protein expression leads to biphasic regulation of the p21 cdk inhibitor and modulation of hepatocyte cell cycle

Hau Nguyen, Maria Mudryj, Moraima Guadalupe, Satya Dandekar

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) Core protein is implicated in viral pathogenesis by the modulation of hepatocyte gene expression and function. To determine the effect of Core protein on the cell-cycle control of hepatocytes, a HepG2 cell line containing a Flag-tagged Core under the control of an inducible promoter was generated. Initial Core protein expression included the presence of unprocessed (191 aa) and processed (173 aa) forms of the Core proteins with the processed form becoming dominant later. Expression of the 191 aa form of Core protein corresponded to an increase in the expression of the p21, a decrease in cdk2-dependent kinase activity, and a decrease in the percentage of cells in S-phase along with an accumulation of cells in the G0/G1 phase of the cell cycle. As the processed form accumulated, the p21 levels started to decline, suggesting that Core protein regulates p21 expression in a biphasic manner. These findings implicate Core protein in potentially modulating hepatocyte cell cycle differentially in the early stages of infection through biphasic regulation of p21 cdk kinase inhibitor.

Original languageEnglish (US)
Pages (from-to)245-253
Number of pages9
JournalVirology
Volume312
Issue number1
DOIs
StatePublished - Jul 20 2003

Fingerprint

Hepatocytes
Cell Cycle
Proteins
Phosphotransferases
Cell Cycle Resting Phase
Hep G2 Cells
G1 Phase
Cell Cycle Checkpoints
S Phase
Hepatitis C virus nucleocapsid protein
Gene Expression
Cell Line
Infection

Keywords

  • Biphasic
  • cdk2
  • Cell cycle
  • Core protein
  • HCV
  • p21

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Hepatitis C virus core protein expression leads to biphasic regulation of the p21 cdk inhibitor and modulation of hepatocyte cell cycle. / Nguyen, Hau; Mudryj, Maria; Guadalupe, Moraima; Dandekar, Satya.

In: Virology, Vol. 312, No. 1, 20.07.2003, p. 245-253.

Research output: Contribution to journalArticle

@article{99aaa1bc4a4c421ebfa1ac4b19725ef1,
title = "Hepatitis C virus core protein expression leads to biphasic regulation of the p21 cdk inhibitor and modulation of hepatocyte cell cycle",
abstract = "Hepatitis C virus (HCV) Core protein is implicated in viral pathogenesis by the modulation of hepatocyte gene expression and function. To determine the effect of Core protein on the cell-cycle control of hepatocytes, a HepG2 cell line containing a Flag-tagged Core under the control of an inducible promoter was generated. Initial Core protein expression included the presence of unprocessed (191 aa) and processed (173 aa) forms of the Core proteins with the processed form becoming dominant later. Expression of the 191 aa form of Core protein corresponded to an increase in the expression of the p21, a decrease in cdk2-dependent kinase activity, and a decrease in the percentage of cells in S-phase along with an accumulation of cells in the G0/G1 phase of the cell cycle. As the processed form accumulated, the p21 levels started to decline, suggesting that Core protein regulates p21 expression in a biphasic manner. These findings implicate Core protein in potentially modulating hepatocyte cell cycle differentially in the early stages of infection through biphasic regulation of p21 cdk kinase inhibitor.",
keywords = "Biphasic, cdk2, Cell cycle, Core protein, HCV, p21",
author = "Hau Nguyen and Maria Mudryj and Moraima Guadalupe and Satya Dandekar",
year = "2003",
month = "7",
day = "20",
doi = "10.1016/S0042-6822(03)00209-5",
language = "English (US)",
volume = "312",
pages = "245--253",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Hepatitis C virus core protein expression leads to biphasic regulation of the p21 cdk inhibitor and modulation of hepatocyte cell cycle

AU - Nguyen, Hau

AU - Mudryj, Maria

AU - Guadalupe, Moraima

AU - Dandekar, Satya

PY - 2003/7/20

Y1 - 2003/7/20

N2 - Hepatitis C virus (HCV) Core protein is implicated in viral pathogenesis by the modulation of hepatocyte gene expression and function. To determine the effect of Core protein on the cell-cycle control of hepatocytes, a HepG2 cell line containing a Flag-tagged Core under the control of an inducible promoter was generated. Initial Core protein expression included the presence of unprocessed (191 aa) and processed (173 aa) forms of the Core proteins with the processed form becoming dominant later. Expression of the 191 aa form of Core protein corresponded to an increase in the expression of the p21, a decrease in cdk2-dependent kinase activity, and a decrease in the percentage of cells in S-phase along with an accumulation of cells in the G0/G1 phase of the cell cycle. As the processed form accumulated, the p21 levels started to decline, suggesting that Core protein regulates p21 expression in a biphasic manner. These findings implicate Core protein in potentially modulating hepatocyte cell cycle differentially in the early stages of infection through biphasic regulation of p21 cdk kinase inhibitor.

AB - Hepatitis C virus (HCV) Core protein is implicated in viral pathogenesis by the modulation of hepatocyte gene expression and function. To determine the effect of Core protein on the cell-cycle control of hepatocytes, a HepG2 cell line containing a Flag-tagged Core under the control of an inducible promoter was generated. Initial Core protein expression included the presence of unprocessed (191 aa) and processed (173 aa) forms of the Core proteins with the processed form becoming dominant later. Expression of the 191 aa form of Core protein corresponded to an increase in the expression of the p21, a decrease in cdk2-dependent kinase activity, and a decrease in the percentage of cells in S-phase along with an accumulation of cells in the G0/G1 phase of the cell cycle. As the processed form accumulated, the p21 levels started to decline, suggesting that Core protein regulates p21 expression in a biphasic manner. These findings implicate Core protein in potentially modulating hepatocyte cell cycle differentially in the early stages of infection through biphasic regulation of p21 cdk kinase inhibitor.

KW - Biphasic

KW - cdk2

KW - Cell cycle

KW - Core protein

KW - HCV

KW - p21

UR - http://www.scopus.com/inward/record.url?scp=0042668538&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042668538&partnerID=8YFLogxK

U2 - 10.1016/S0042-6822(03)00209-5

DO - 10.1016/S0042-6822(03)00209-5

M3 - Article

C2 - 12890637

AN - SCOPUS:0042668538

VL - 312

SP - 245

EP - 253

JO - Virology

JF - Virology

SN - 0042-6822

IS - 1

ER -