Soraphen A: a probe for investigating the role of de novo lipogenesis during viral infection

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DOIResolve DOI: http://doi.org/10.1021/acsinfecdis.5b00019
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TypeArticle
Journal titleACS Infectious Diseases
ISSN2373-8227
Volume1
Issue3
Pages130134
SubjectCARS; Coherent anti-Stokes Raman spectroscopy; HCV; Hepatitis C virus; Lipids
AbstractMany viruses including the hepatitis C virus (HCV) induce changes to the infected host cell metabolism that include the up-regulation of lipogenesis to create a favorable environment for the virus to propagate. The enzyme acetyl-CoA carboxylase (ACC) polymerizes to form a supramolecular complex that catalyzes the rate-limiting step of de novo lipogenesis. The small molecule natural product Soraphen A (SorA) acts as a nanomolar inhibitor of acetyl-CoA carboxylase activity through disruption of the formation of long highly active ACC polymers from less active ACC dimers. We have shown that SorA inhibits HCV replication in HCV cell culture models expressing subgenomic and full-length replicons (IC₅₀ = 5 nM) as well as a cell culture adapted virus. Using coherent anti-Stokes Raman scattering (CARS) microscopy, we have shown that SorA lowers the total cellular lipid volume in hepatoma cells, consistent with a reduction in de novo lipogenesis. Furthermore, SorA treatment was found to depolymerize the ACC complexes into less active dimers. Taken together, our results suggest that SorA treatment reverses HCV-induced lipid accumulation and demonstrate that SorA is a valuable probe to study the roles of ACC polymerization and enzymatic activity in viral pathogenesis.
Publication date
PublisherACS Publications
LanguageEnglish
AffiliationMedical Devices; National Research Council Canada
Peer reviewedYes
NPARC number23000357
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Record identifier739a7809-7cbb-4f94-b5a8-fe7b0c0ac472
Record created2016-07-08
Record modified2016-07-08
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