Dengue Virus Uses a Non-Canonical Function of the Host GBF1-Arf-COPI System for Capsid Protein Accumulation on Lipid Droplets

NESTOR G IGLESIAS; JUAN A. MONDOTTE; LAURA A. BYK; FEDERICO A. DE MAIO; MARCELO M. SAMSA; CECILIA ALVAREZ; ANDREA GAMARNIK

TRAFFIC

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2015

1398-9219

Dengue viruses cause the most important human viral disease trans-mitted by mosquitoes. In recent years, a great deal has been learnedabout molecular details of dengue virus genome replication; however,little is known about genome encapsidation and the functions of the viralcapsid protein. During infection, dengue virus capsid progressively accu-mulates around lipid droplets (LDs) by an unknown mechanism. Here,we examined the process by which the viral capsid is transported fromthe endoplasmic reticulum (ER) membrane, where the protein is synthe-sized, to LDs. Using different methods of intervention, we found that theGBF1-Arf1/Arf4-COPI pathway is necessary for capsid transport to LDs,while the process is independent of both COPII components and Golgiintegrity. The transport was sensitive to Brefeldin A, while a drug resis-tant form of GBF1 was sufficient to restore capsid subcellular distributionin infected cells. The mechanism by which LDs gain or lose proteins is stillan open question. Our results support a model in which the virus uses anon-canonical function of the COPI system for capsid accumulation onLDs, providing new ideas for antiviral strategies.