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

IGLESIAS N.. ; MONDOTTE J.; BYK L.; DE MAIO F. ; SAMSA M.; ALVAREZ C.; GAMARNIK A.

TRAFFIC

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2015

1398-9219

Dengue viruses cause the mostimportant human viral disease transmitted by mosquitoes. In recent years, agreat deal has been learned about molecular details of dengue virus genomereplication; however, little is known about genome encapsidation and thefunctions of the viral capsid protein. During infection, dengue virus capsid progressivelyaccumulates around lipid droplets by an unknown mechanism. Here, we examinedthe process by which the viral capsid is transported from the ER membrane, wherethe protein is synthesized, to lipid droplets. Using different methods ofintervention, we found that the GBF1-Arf1/Arf4-COPI pathway is necessary forcapsid transport to lipid droplets, while the process is independent of both COPIIcomponents and Golgi integrity. The transport was sensitive to brefeldin A, whilea drug resistant form of GBF1 was sufficient to restore capsid subcellulardistribution in infected cells. The mechanism by which lipid droplets gain orlose proteins is still an open question. Our results support a model in whichthe virus uses a non-canonical function of the COPI system for capsid accumulationon lipid droplets, providing new ideas for antiviral strategies.