Hepatitis B Virus Deregulates the Cell Cycle To Promote Viral Replication and a Premalignant Phenotype

Journal of Virology
Yuchen XiaT Jake Liang

Abstract

Hepatitis B virus (HBV) infection is a major health problem worldwide, and chronically infected individuals are at high risk of developing cirrhosis and hepatocellular carcinoma (HCC). The molecular mechanisms whereby HBV causes HCC are largely unknown. Using a biologically relevant system of HBV infection of primary human hepatocytes (PHHs), we studied how HBV perturbs gene expression and signaling pathways of infected hepatocytes and whether these effects are relevant to productive HBV infection and HBV-associated HCC. Using a human growth factor antibody array, we first showed that HBV infection induced a distinct profile of growth factor production by PHHs, marked particularly by significantly lower levels of the transforming growth factor β (TGF-β) family of proteins in the supernatant. Transcriptome profiling next revealed multiple changes in cell proliferation and cell cycle control pathways in response to HBV infection. A human cell cycle PCR array validated deregulation of more than 20 genes associated with the cell cycle in HBV-infected PHHs. Cell cycle analysis demonstrated that HBV-infected PHHs are enriched in the G2/M phase compared to the predominantly G0/G1 phase of cultured PHHs. HBV proviral host factors, such...Continue Reading

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Citations

Mar 29, 2019·Life Science Alliance·Peter Ac WingJane A McKeating
Feb 6, 2020·Viruses·Kristi L TurtonTrushar R Patel
Mar 13, 2020·The Journal of Clinical Investigation·Xiaoming ChengT Jake Liang
Aug 21, 2019·Frontiers in Oncology·Aarti Kolluri, Mitchell Ho
Aug 14, 2020·International Journal of Molecular Sciences·Kaku GotoKunitada Shimotohno
Aug 2, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kirk J Wangensteen, Kyong-Mi Chang
Dec 3, 2020·Journal of Cellular and Molecular Medicine·Mingjie XieMin Zheng
Aug 8, 2021·International Journal of Molecular Sciences·Hugo Christian Monroy-RamirezJuan Armendariz-Borunda

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