Lipids Go Viral

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Science  15 Oct 2010:
Vol. 330, Issue 6002, pp. 297
DOI: 10.1126/science.330.6002.297-c
CREDIT: HEATON ET AL., PROC. NATL. ACAD. SCI. U.S.A. 107, 17345 (2010)

Host cell membranes and their lipid constituents play an essential role in the life cycle of a group of single-stranded RNA viruses called flaviviruses. Lipids help the viruses enter the cell, establish intracellular sites for replication of their RNA genomes, and assemble the nascent RNA into viral particles, which exit the cell as infectious entities. Conceivably, a better understanding of the mechanisms by which the viruses co-opt host cell membranes for their own gain could lead to new antiviral therapies. Progress along these lines was recently reported by independent research groups studying two medically important flaviviruses. Studying the fever-causing dengue virus, Heaton et al. found that viral protein NS3 binds to fatty acid synthase (FASN, red at left), a host enzyme that makes fatty acids, and relocalizes it to sites of viral RNA replication (green) in the endoplasmic reticulum, resulting in de novo synthesis of lipids near the replication complexes. In analogous work on hepatitis C virus (HCV), which can cause severe liver damage, Herker et al. found that the viral nucleocapsid core binds to diacylglycerol acyltranferase-1 (DGAT1), a host enzyme that participates in lipid droplet synthesis. This interaction results in recruitment of HCV RNA replication complexes to lipid droplets near the ER, which are crucial for assembly of infectious HCV particles. Interestingly, both FASN and DGAT1 have already been studied as possible drug targets for obesity-related diseases.

Proc. Natl. Acad. Sci. U.S.A. 107, 17345 (2010); Nat. Med. 16, 10.1038/nm.2238 (2010).

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