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Virology

Greasing the wheels of replication

Nature Reviews Microbiology volume 8, pages 758–759 (2010)Cite this article

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recruitment of FASN to the ER-associated replication complexes was coupled with an increase in fatty acid biosynthesis

To identify host cell factors that are important for DENV replication, Heaton et al. used a small interfering RNA library that targets genes involved in host cell pathways which are known to be crucial for the replication of other viruses. Most of the genes that they identified were clustered into three cellular pathways: actin polymerization (CDC42 and DIAPH1), ER stress and autophagy (ATF6, XBP1 and ATG12) and fatty acid biosynthesis (ACACA and FASN). From those hits identified, the authors went on to further characterize the role of the FASN-encoded fatty acid synthase in DENV replication. In uninfected cells, FASN exhibited a diffuse localization, but on infection with DENV the localization changed and FASN was observed to colocalize with DENV markers on the ER. This redistribution was found to rely on the interaction of FASN with DENV non-structural protein 3 (NS3). Using 14C-radiolabelled acetate or malonyl-CoA (indirect and direct substrates of FASN, respectively), the authors observed that recruitment of FASN to the ER-associated replication complexes was coupled with an increase in fatty acid biosynthesis, which indicates that DENV co-opts this pathway for efficient replication.

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ORIGINAL RESEARCH PAPER

  1. Heaton, N. S. et al. Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis. Proc. Natl Acad. Sci. USA 20 Sep 2010 (doi: 10.1073/pnas.1010811107)

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  1. Andrew Jermy
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Jermy, A. Greasing the wheels of replication. Nat Rev Microbiol 8, 758–759 (2010). https://doi.org/10.1038/nrmicro2463

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