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J Gen Virol 89 (2008), 1225-1230; DOI 10.1099/vir.0.83491-0

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Short Communication

Activation of sterol regulatory element-binding protein 1c and fatty acid synthase transcription by hepatitis C virus non-structural protein 2

Jae-Ku Oem1,{dagger}, Candice Jackel-Cram1,{dagger}, Yi-Ping Li1,{ddagger}, Yan Zhou1, Jin Zhong2, Hitoshi Shimano3, Lorne A. Babiuk1,4 and Qiang Liu1

1 Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada
2 Institut Pasteur of Shanghai, Shanghai, PR China
3 University of Tsukuba, Tsukuba City, Ibaraki, Japan
4 University of Alberta, Edmonton, Alberta, Canada

Correspondence
Qiang Liu
qiang.liu{at}usask.ca

Transcriptional factor sterol regulatory element-binding protein 1c (SREBP-1c) activates the transcription of lipogenic genes, including fatty acid synthase (FAS). Hepatitis C virus (HCV) infection is often associated with lipid accumulation within the liver, known as steatosis in the clinic. The molecular mechanisms of HCV-associated steatosis are not well characterized. Here, we showed that HCV non-structural protein 2 (NS2) activated SREBP-1c transcription in human hepatic Huh-7 cells as measured by using a human SREBP-1c promoter–luciferase reporter plasmid. We further showed that sterol regulatory element (SRE) and liver X receptor element (LXRE) in the SREBP-1c promoter were involved in SREBP-1c activation by HCV NS2. Furthermore, expression of HCV NS2 resulted in the upregulation of FAS transcription. We also showed that FAS upregulation by HCV NS2 was SREBP-1-dependent since deleting the SRE sequence in a FAS promoter and expressing a dominant-negative SREBP-1 abrogated FAS promoter upregulation by HCV NS2. Taken together, our results suggest that HCV NS2 can upregulate the transcription of SREBP-1c and FAS, and thus is probably a contributing factor for HCV-associated steatosis.

{dagger}These authors contributed equally to this work.

{ddagger}Present address: National Veterinary Institute, Technical University of Denmark, Hangøvej, Århus N, Denmark.




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C.-Y. Park, H.-J. Jun, T. Wakita, J. H. Cheong, and S. B. Hwang
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[Abstract] [Full Text] [PDF]




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