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

Authors
Iglesias, Nestor Gabriel; Mondotte, Juan Alberto; Byk, Laura Andrea; de Maio, Federico Andres; Samsa, Marcelo Mario Alejandro; Alvarez, Cecilia Ines; Gamarnik, Andrea Vanesa
Publication Year
2015
Language
English
Format
article
Status
Published version
Description
Dengue viruses cause the most important human viral disease transmittedby 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 theviral capsid protein. During infection, dengue virus capsid progressivelyaccumulates around lipid droplets (LDs) by an unknown mechanism.Here, we examined the process by which the viral capsid is transportedfrom the endoplasmic reticulum (ER) membrane, where the protein issynthesized, to LDs. Using different methods of intervention, we foundthat the GBF1-Arf1/Arf4-COPI pathway is necessary for capsid transportto LDs, while the process is independent of both COPII componentsand Golgi integrity. The transport was sensitive to Brefeldin A, while adrug resistant form of GBF1 was sufficient to restore capsid subcellulardistribution in infected cells. The mechanism by which LDs gain or loseproteins is still an open question. Our results support a model in whichthe virus uses a non-canonical function of the COPI system for capsidaccumulation on LDs, providing new ideas for antiviral strategies.
Fil: Iglesias, Nestor Gabriel. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mondotte, Juan Alberto. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Byk, Laura Andrea. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: de Maio, Federico Andres. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Samsa, Marcelo Mario Alejandro. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Alvarez, Cecilia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Bioquímica Clínica E Inmunología; Argentina
Fil: Gamarnik, Andrea Vanesa. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Subject
capsid protein
COPI
dengue virus
flavivirus
GBF1
lipid droplets
Biología Celular, Microbiología
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/7808