An important role of SREBP-1 in HBV and HCV co-replication inhibition by PTEN

Qi Wu; Zhubing Li; Qiang Liu

doi:10.1016/j.virol.2018.05.011

An important role of SREBP-1 in HBV and HCV co-replication inhibition by PTEN

Virology. 2018 Jul:520:94-102. doi: 10.1016/j.virol.2018.05.011. Epub 2018 May 26.

Authors

Qi Wu¹, Zhubing Li², Qiang Liu³

Affiliations

¹ Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan 120 Veterinary Road, Saskatoon, Saskatchewan, Canada S7N 5E3; Department of Veterinary Microbiology, University of Saskatchewan, Canada.
² Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan 120 Veterinary Road, Saskatoon, Saskatchewan, Canada S7N 5E3; School of Public Health Vaccinology and Immunotherapeutics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
³ Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan 120 Veterinary Road, Saskatoon, Saskatchewan, Canada S7N 5E3; Department of Veterinary Microbiology, University of Saskatchewan, Canada; School of Public Health Vaccinology and Immunotherapeutics, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. Electronic address: qiang.liu@usask.ca.

PMID: 29803738
DOI: 10.1016/j.virol.2018.05.011

Abstract

HBV HCV co-infection leads to more severe liver diseases including liver cancer than mono-infections. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor, inhibits sterol regulatory element binding protein-1 (SREBP-1). In this study, we characterized the effect of the PTEN - SREBP-1 pathway on HBV HCV co-replication in a cellular model. We found that HBV and HCV can co-replicate in Huh-7 cells with no interference. Overexpression of PTEN inhibits, whereas PTEN knockdown enhances, HBV replication as well as HBV and HCV co-replication. Knocking down SREBP-1 decreases HBV replication in an HBx-dependent manner. SREBP-1 knockdown also decreases HCV replication. PTEN knockdown is concomitant with increased nuclear SREBP-1 levels. PTEN and SREBP-1 double knockdown results in intermediate levels of HBV and HCV replication in mono- and co-replication scenarios. Taken together, we demonstrated, for the first time, that the PTEN - SREBP-1 pathway can regulate HBV HCV co-replication.

Keywords: Co-replication; HBV; HCV; PTEN; SREBP-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular / virology
Cell Line, Tumor
DNA Replication
Gene Knockdown Techniques
Hepacivirus / physiology*
Hepatitis B virus / physiology*
Hepatocytes / virology
Humans
Liver Neoplasms / virology
PTEN Phosphohydrolase / deficiency
PTEN Phosphohydrolase / genetics*
PTEN Phosphohydrolase / metabolism*
Sterol Regulatory Element Binding Protein 1 / deficiency
Sterol Regulatory Element Binding Protein 1 / genetics
Sterol Regulatory Element Binding Protein 1 / metabolism*
Virus Replication*

Substances

Sterol Regulatory Element Binding Protein 1
PTEN Phosphohydrolase
PTEN protein, human

Grants and funding

NHC-142832/CIHR/Canada