title: Dengue Virus Uses a Non-Canonical Function of the Host GBF1-Arf-COPI System for Capsid Protein Accumulation on Lipid Droplets.
abstract: Dengue viruses cause the most important human viral disease transmitted by mosquitoes. In recent years, a great deal has been learned about molecular details of dengue virus genome replication; however, little is known about genome encapsidation and the functions of the viral capsid protein. During infection, dengue virus capsid progressively accumulates around lipid droplets (LDs) by an unknown mechanism. Here, we examined the process by which the viral capsid is transported from the endoplasmic reticulum (ER) membrane, where the protein is synthesized, to LDs. Using different methods of intervention, we found that the GBF1-Arf1/Arf4-COPI pathway is necessary for capsid transport to LDs, while the process is independent of both COPII components and Golgi integrity. The transport was sensitive to Brefeldin A, while a drug resistant form of GBF1 was sufficient to restore capsid subcellular distribution in infected cells. The mechanism by which LDs gain or lose proteins is still an open question. Our results support a model in which the virus uses a non-canonical function of the COPI system for capsid accumulation on LDs, providing new ideas for antiviral strategies.
authors.affiliation: Fundación Instituto Leloir-CONICET, Avenida Patricias Argentinas 435, Buenos Aires, 1405, Argentina.
authors.forename: Nestor G
authors.initials: NG
authors.lastname: Iglesias
authors.affiliation: Fundación Instituto Leloir-CONICET, Avenida Patricias Argentinas 435, Buenos Aires, 1405, Argentina.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Mondotte
authors.affiliation: Fundación Instituto Leloir-CONICET, Avenida Patricias Argentinas 435, Buenos Aires, 1405, Argentina.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Byk
authors.affiliation: Fundación Instituto Leloir-CONICET, Avenida Patricias Argentinas 435, Buenos Aires, 1405, Argentina.
authors.forename: Federico A
authors.initials: FA
authors.lastname: De Maio
authors.affiliation: Fundación Instituto Leloir-CONICET, Avenida Patricias Argentinas 435, Buenos Aires, 1405, Argentina.
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Samsa
authors.affiliation: Centro de Investigaciones en Bioquímica Clínica e Inmunología-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, UNC, 5000, Córdoba, Argentina.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Alvarez
authors.affiliation: Fundación Instituto Leloir-CONICET, Avenida Patricias Argentinas 435, Buenos Aires, 1405, Argentina.
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Gamarnik
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism*; D036022:Capsid Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D020755:Coat Protein Complex I / Q000378:metabolism*; D003716:Dengue Virus / Q000378:metabolism* / Q000472:pathogenicity; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000821:virology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism* / Q000821:virology; D021381:Protein Transport
chemical_list: D036022:Capsid Proteins; D020755:Coat Protein Complex I; C120445:GBF1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D020823:ADP-Ribosylation Factor 1
keywords: COPI; GBF1; capsid protein; dengue virus; flavivirus; lipid droplets