Hepatitis C virus nonstructural proteins inhibit apolipoprotein B100 secretion.
Host genes involved in lipid metabolism are differentially regulated during the early stages of hepatitis C virus (HCV) infection. The majority of lipids synthesized in the liver are exported to other tissues in the form of lipoproteins. The formation of these lipoproteins is dependent upon the association of triglycerides with apolipoprotein B100. Using the HCV subgenomic replicon expression system, we show that secretion of apoB100 is significantly reduced. Inhibition of apoB100 degradation by ALLN did not improve secretion. Triglyceride levels as well as microsomal triglyceride transfer protein mRNA and activity levels were reduced in replicon-expressing cells, indicating potential reasons for the observed decrease. Further evidence is presented for the interaction between the HCV nonstructural protein 5A and apoB100. These results provide further insight into the alteration of lipid metabolism by HCV.
Domitrovich
Angela M
AM
Department of Medicine, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093-0803, USA.
Felmlee
Daniel J
DJ
Siddiqui
Aleem
A
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter; D016679:Genome, Viral; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D007976:Leupeptins / Q000494:pharmacology; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D019301:Oleic Acid / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D008055:Lipids; D019301:Oleic Acid; D012333:RNA, Messenger; D014280:Triglycerides; D017361:Viral Nonstructural Proteins; C106092:microsomal triglyceride transfer protein; C063261:acetylleucyl-leucyl-norleucinal; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase