Altered proteolysis and global gene expression in hepatitis B virus X transgenic mouse liver

Zongyi Hu, Zhensheng Zhang, Jin Woo Kim, Ying Huang, T. Jake Liang

Research output: Contribution to journalArticle

Abstract

Hepatitis B virus X (HBX) is essential for the productive infection of hepatitis B virus (HBV) in vivo and has a pleiotropic effect on host cells. We have previously demonstrated that the proteasome complex is a cellular target of HBX, that HBX alters the proteolytic activity of proteasome in vitro, and that inhibition of proteasome leads to enhanced viral replication, suggesting that HBX and proteasome interaction plays a crucial role in the life cycle and pathogenesis of HBV. In the present study, we tested the effect of HBX on the proteasome activities in vivo in a transgenic mouse model in which HBX expression is developmentally regulated by the mouse major urinary promoter in the liver. In addition, microarray analysis was performed to examine the effect of HBX expression on the global gene expression profile of the liver. The results showed that the peptidase activities of the proteasome were reduced in the HBX transgenic mouse liver, whereas the activity of another cellular protease was elevated, suggesting a compensatory mechanism in protein degradation. In the microarray analysis, diverse genes were altered in the HBX mouse livers and the number of genes with significant changes increased progressively with age. Functional clustering showed that a number of genes involved in transcription and cell growth were significantly affected in the HBX mice, possibly accounting for the observed pleiotropic effect of HBX. In particular, insulin-like growth factor-binding protein 1 was down-regulated in the HBX mouse liver. The down-regulation was similarly observed during acute woodchuck hepatitis virus infection. Other changes including up-regulation of proteolysis-related genes may also contribute to the profound alterations of liver functions in HBV infection.

Original languageEnglish (US)
Pages (from-to)1405-1413
Number of pages9
JournalJournal of Virology
Volume80
Issue number3
DOIs
StatePublished - Feb 2006
Externally publishedYes

Fingerprint

Hepatitis B virus
proteolysis
Transgenic Mice
Proteolysis
genetically modified organisms
Gene Expression
gene expression
liver
Liver
mice
proteasome endopeptidase complex
Proteasome Endopeptidase Complex
Virus Diseases
Microarray Analysis
Genes
Woodchuck hepatitis virus
Peptide Hydrolases
genes
Woodchuck Hepatitis B Virus
infection

ASJC Scopus subject areas

  • Immunology

Cite this

Altered proteolysis and global gene expression in hepatitis B virus X transgenic mouse liver. / Hu, Zongyi; Zhang, Zhensheng; Kim, Jin Woo; Huang, Ying; Liang, T. Jake.

In: Journal of Virology, Vol. 80, No. 3, 02.2006, p. 1405-1413.

Research output: Contribution to journalArticle

Hu, Zongyi ; Zhang, Zhensheng ; Kim, Jin Woo ; Huang, Ying ; Liang, T. Jake. / Altered proteolysis and global gene expression in hepatitis B virus X transgenic mouse liver. In: Journal of Virology. 2006 ; Vol. 80, No. 3. pp. 1405-1413.
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