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Mosquito-borne flavivirus infections cause changes in host lipid metabolism. For example, scientists found that the dengue virus, which has no known antiviral treatments, recruits host fatty acid synthase to aid in viral replication. In a recent Journal of Biological Chemistry , Julia Hehner at Philipps University Marburg and a team in Germany investigated the reliance of various flaviviruses on host fatty acid elongases and desaturases, key enzymes in the biosynthesis of monounsaturated and polyunsaturated fatty acids.

National Institute of Allergy and Infectious Diseases

3D renderings of dengue virions

Working with a human hepatic cell line, the authors used RNA interference to individually knock down each fatty acid elongase and desaturase, enzymes that catalyze specific steps for producing fatty acids of different lengths. They exposed the cell lines to dengue, Zika, West Nile, yellow fever and tick-borne encephalitis viruses to measure viral replication. Only dengue virus showed sensitivity to the knockdowns, indicating that this virus relies on fatty acids of specific lengths, while the other viruses can compensate for the loss of one enzyme. Knocking down either the ultra-long-chain elongase ELOVL4 or desaturase FADS2 caused decreased dengue viral titers.

The researchers determined that ELOVL4 knockdown led to slightly lower viral protein levels in the infected cells, possibly signaling ELOVL4 involvement in delaying RNA replication. Surprisingly, the cells lacking FADS2 showed a slight increase in viral protein levels. The authors next measured plaque formation of dengue virus particles produced by the knockdown cell lines and found that cells lacking FADS2 produced viral particles with diminished infectivity. This indicates that FADS2 may promote lipid synthesis necessary for dengue virion assembly.

Future studies will help address the mechanisms behind the observed increase in viral protein levels upon FADS2 knockdown. Further experiments will also help researchers fill in the mechanistic details about how the ultra-long-chain fatty acids produced by ELOVL4 enhance dengue virus infectivity.