The human fatty acid synthase: a new therapeutic target for coxsackievirus B3-induced diseases?
Coxsackievirus is linked to a large variety of severe human and animal diseases such as myocarditis. The interplay between host factors and virus components is crucial for the fate of the infected cells. However, host proteins which may play a role in coxsackievirus-induced diseases are ill-defined. Two-dimensional gel electrophoresis of protein extracts obtained from coxsackievirus B3 (CVB3)-infected and uninfected HeLa or HepG2 cells combined with spot analysis revealed several proteins which are exclusively up-regulated in infected cells. One of these proteins was identified as the fatty acid synthase (FAS). By using cerulenin and C75, two known inhibitors of FAS we were able to significantly block CVB3 replication. FAS appears to be directly involved in CVB3-caused pathology and is therefore suitable as a therapeutic target in CVB3-induced diseases.
Rassmann
Alexander
A
Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knoell-Institute, Department of Cell and Molecular Biology, Beutenbergstrasse 11a, D-07745 Jena, Germany.
Henke
Andreas
A
Jarasch
Nadine
N
Lottspeich
Friedrich
F
Saluz
Hans-Peter
HP
Munder
Thomas
T
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D002569:Cerulenin / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D029822:Enterovirus B, Human / Q000254:growth & development*; D004791:Enzyme Inhibitors; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D015854:Up-Regulation; D014779:Virus Replication / Q000187:drug effects
C406734:4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D002569:Cerulenin; D064429:Fatty Acid Synthases; D015107:4-Butyrolactone