Dengue virus commandeers fat droplets inside cells in order to replicate and spread, new research shows. Using an anti-obesity drug that reduces the number of these fat droplets slows the spread of the virus, according to work by HHMI international research scholar Andrea V. Gamarnik and her colleagues.
Dengue virus contains a single RNA strand, which is replicated inside infected cells and then packaged into new viral particles. To figure out how the virus commands infected cells to do the packaging, the scientists tagged capsid proteins—found in the viral particles—with fluorescent labels. Under the microscope, the capsid proteins encircled fat droplets—sacs involved in producing and storing lipids.
Gamarnik's lab group then mutated different parts of the capsid protein to determine which section was attracted to the fat droplets. When they mutated the middle region, the capsid proteins could no longer bind to the fat droplets and the virus's spread slowed drastically.
To find a mimic for this viral slowdown, the researchers turned to a drug designed for treating obesity that decreases the number of fat droplets per cell. The drug worked to slow dengue—the number of new viral particles per cell dropped more than 100-fold.
“This is an interesting and new example of how a virus uses a specific organelle in the cell for its own purpose,” says Gamarnik. “It opens the door for new ways to think about antiviral strategies.”
Published in the October 2009 issue of PLoS Pathogens, the work also shows that dengue virus spurs the cell into making more fat droplets for it to use. Since other members of the mosquito-borne Flavivirus genus—including West Nile virus and yellow fever—share with dengue the use of capsid-encased particles to spread, Gamarnik thinks these other viruses may use the same mechanism.