Cre-estrogen receptor-mediated hepatitis C virus structural protein expression in mice

Batbayar Tumurbaatar, Yixiao Sun, Tehsheng Chan, Jiaren Sun

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Hepatocyte apoptosis is an important feature of liver injury in hepatitis C virus (HCV) infection. However, the mechanism of apoptosis and consequences on disease progression in vivo have not been investigated fully in part due to the lack of adequate small animal models. In this study, transgenic (tg) mice were produced that express conditionally HCV structural proteins (core, E1, E2 and p7) in the liver following Cre-mediated DNA recombination. Using a novel Cre-estrogen receptor fusion protein (Cre-ER) induction strategy, tamoxifen was injected intraperitoneally (i.p.), which induced Cre nuclear translocation, transgene recombination and HCV protein expression in the liver. Hepatic expression of HCV core and envelope proteins resulted in increased hepatocyte apoptosis, detected by the TUNEL assay, between 7 and 33 days after induction. These results were confirmed by the presence of increased levels of apoptosis-associated cytokeratin 18 (CK-18) in the sera of the same animals. The presence of cleaved caspase-3 and elevated levels of CHOP/GADD153 in the liver suggests an endoplasmic reticulum (ER) stress-associated apoptosis mechanism. This study suggests an in vivo correlation between HCV structural protein expression, ER stress and hepatocyte apoptosis, implicating a potentially important mechanism of HCV pathogenesis.

Original languageEnglish (US)
Pages (from-to)5-13
Number of pages9
JournalJournal of Virological Methods
Volume146
Issue number1-2
DOIs
StatePublished - Dec 2007

Fingerprint

Viral Structural Proteins
Hepacivirus
Estrogen Receptors
Apoptosis
Liver
Hepatocytes
Endoplasmic Reticulum Stress
Genetic Recombination
Viral Envelope Proteins
Keratin-18
In Situ Nick-End Labeling
Virus Diseases
Tamoxifen
Transgenes
Caspase 3
Transgenic Mice
Disease Progression
Animal Models
DNA
Wounds and Injuries

Keywords

  • Animal model and liver injury
  • Transgenic mouse
  • Viral hepatitis

ASJC Scopus subject areas

  • Virology

Cite this

Cre-estrogen receptor-mediated hepatitis C virus structural protein expression in mice. / Tumurbaatar, Batbayar; Sun, Yixiao; Chan, Tehsheng; Sun, Jiaren.

In: Journal of Virological Methods, Vol. 146, No. 1-2, 12.2007, p. 5-13.

Research output: Contribution to journalArticle

Tumurbaatar, Batbayar ; Sun, Yixiao ; Chan, Tehsheng ; Sun, Jiaren. / Cre-estrogen receptor-mediated hepatitis C virus structural protein expression in mice. In: Journal of Virological Methods. 2007 ; Vol. 146, No. 1-2. pp. 5-13.
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