Host fatty acids enhance dengue virus infectivity
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 article, 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.
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.
Enjoy reading ASBMB Today?
Become a member to receive the print edition four times a year and the digital edition monthly.
Learn moreGet the latest from ASBMB Today
Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.
Latest in Science
Science highlights or most popular articles
Differences in pili structure modulate bacterial behavior
Researchers demonstrate how small changes in the structure of hair-like protein appendages can affect the behavior of Acinetobacter bacteria.
Cholesterol regulatory genes predict liver transplant outcomes
Researchers identify a link between cholesterol-regulating genes and liver transplant success, which could improve donor screening and patient outcomes.
Lipid signatures for a rare neurological disorder
Researchers find distinct lipid patterns linked to a rare autoimmune neurological disorder, offering hope for effective targeted therapies for patients.
Disease-linked mutations disrupt protein phase behavior
Researchers find that pathogenic missense mutations are enriched threefold in phrase-separating intrinsically disordered regions of proteins.
The dual role of asprosin in chronic fatty liver disease
Researchers uncover a hormone called asprosin that may serve as a potential biomarker for the diagnosis of chronic fatty liver disease and monitoring disease progression.
Novel inhibitor targets RAS-driven cancers
Researchers in Louisville identify a small-molecule drug that blocks RALGEF signaling downstream of mutant RAS. The compound suppresses tumor growth with low toxicity, revealing a new therapeutic strategy for RAS-driven malignancies.