Article
- The EMBO Journal (2002) 21, 3980 - 3988
- doi:10.1093/emboj/cdf414
Subject Categories:
Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets
John McLauchlan1, Marius K. Lemberg2, Graham Hope1 and Bruno Martoglio2
- MRC Virology Unit, Division of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, UK
- Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), ETH Hoenggerberg, 8093 Zürich, Switzerland
Correspondence to:
Bruno Martoglio, E-mail: bruno.martoglio@bc.biol.ethz.ch
Received 18 April 2002; Accepted 14 June 2002; Revised 14 June 2002
Abstract
Hepatitis C virus (HCV) is the major causative pathogen associated with liver cirrhosis and hepatocellular carcinoma. The virus has a positive-sense RNA genome encoding a single polyprotein with the virion components located in the N-terminal portion. During biosynthesis of the polyprotein, an internal signal sequence between the core protein and the envelope protein E1 targets the nascent polypeptide to the endoplasmic reticulum (ER) membrane for translocation of E1 into the ER. Following membrane insertion, the signal sequence is cleaved from E1 by signal peptidase. Here we provide evidence that after cleavage by signal peptidase, the signal peptide is further processed by the intramembrane-cleaving protease SPP that promotes the release of core protein from the ER membrane. Core protein is then free for subsequent trafficking to lipid droplets. This study represents an example of a potential role for intramembrane proteolysis in the maturation of a viral protein.
Keywords:
- aspartic protease,
- HCV,
- lipid metabolism,
- SPP,
- viral polyprotein processing
