Activation of sterol regulatory element-binding protein 1c and fatty acid synthase transcription by hepatitis C virus non-structural protein 2.
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.
Oem
Jae-Ku
JK
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada.
Jackel-Cram
Candice
C
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada.
Li
Yi-Ping
YP
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada.
Zhou
Yan
Y
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada.
Zhong
Jin
J
Institut Pasteur of Shanghai, Shanghai, PR China.
Shimano
Hitoshi
H
University of Tsukuba, Tsukuba City, Ibaraki, Japan.
Babiuk
Lorne A
LA
University of Alberta, Edmonton, Alberta, Canada.|Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada.
Liu
Qiang
Q
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada.
D019677:Artificial Gene Fusion; D002460:Cell Line; D064429:Fatty Acid Synthases / Q000096:biosynthesis*; D017930:Genes, Reporter; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D051779:Sterol Regulatory Element Binding Proteins / Q000096:biosynthesis*; D014158:Transcription, Genetic; D017361:Viral Nonstructural Proteins / Q000502:physiology*
C097010:NS2 protein, Hepatitis C virus; D051779:Sterol Regulatory Element Binding Proteins; D017361:Viral Nonstructural Proteins; D008156:Luciferases; D064429:Fatty Acid Synthases