%0 Journal Article %A Oem, Jae-Ku %A Jackel-Cram, Candice %A Li, Yi-Ping %A Zhou, Yan %A Zhong, Jin %A Shimano, Hitoshi %A Babiuk, Lorne A. %A Liu, Qiang %T Activation of sterol regulatory element-binding protein 1c and fatty acid synthase transcription by hepatitis C virus non-structural protein 2 %D 2008 %J Journal of General Virology, %V 89 %N 5 %P 1225-1230 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.83491-0 %I Microbiology Society, %X 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. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.83491-0