Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.chembiol.2013.03.014
Title: Modulation of fatty acid synthase enzyme activity and expression during hepatitis C virus replication
Authors: Nasheri, N.
Joyce, M.
Rouleau, Y.
Yang, P.
Yao, S. 
Tyrrell, D.L.
Pezacki, J.P.
Issue Date: 18-Apr-2013
Citation: Nasheri, N., Joyce, M., Rouleau, Y., Yang, P., Yao, S., Tyrrell, D.L., Pezacki, J.P. (2013-04-18). Modulation of fatty acid synthase enzyme activity and expression during hepatitis C virus replication. Chemistry and Biology 20 (4) : 570-582. ScholarBank@NUS Repository. https://doi.org/10.1016/j.chembiol.2013.03.014
Abstract: The hepatitis C virus (HCV) induces alterations of host cells to facilitate its life cycle. Fatty acid synthase (FASN) is a multidomain enzyme that plays a key role in the biosynthesis of fatty acids and is upregulated during HCV infection. Herein, we applied activity-based protein profiling (ABPP) that allows for the identification of differentially active enzymes in complex proteomic samples, to study the changes in activity of FASN during HCV replication. For this purpose, we used an activity-based probe based on the FASN inhibitor Orlistat, and observed an increase in the activity of FASN in the presence of a subgenomic and a genomic HCV replicon as well as in chimeric SCID/Alb-uPA mice infected with HCV genotype 1a. To study the molecular basis for this increase in FASN activity, we overexpressed individual HCV proteins in Huh7 cells and observed increased expression and activity of FASN in the presence of core and NS4B, as measured by western blots and ABPP, respectively. Triglyceride levels were also elevated in accordance with FASN expression and activity. Lastly, immunofluorescence and ABPP imaging analyses demonstrated that while the abundance and activity of FASN increases significantly in the presence of HCV, its localization does not change. Together these data suggest that the HCV-induced production of fatty acids and neutral lipids is provided by an increase in FASN abundance and activity that is sufficient to allow HCV propagation without transporting FASN to the replication complexes. © 2013 Elsevier Ltd.
Source Title: Chemistry and Biology
URI: http://scholarbank.nus.edu.sg/handle/10635/76577
ISSN: 10745521
DOI: 10.1016/j.chembiol.2013.03.014
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.