title: Dengue virus capsid protein interacts specifically with very low-density lipoproteins.
abstract: Dengue affects millions of people worldwide. No specific treatment is currently available, in part due to an incomplete understanding of the viral components' interactions with host cellular structures. We tested dengue virus (DENV) capsid protein (C) interaction with low- and very low-density lipoproteins (LDL and VLDL, respectively) using atomic force microscopy-based force spectroscopy, dynamic light scattering, NMR and computational analysis. Data reveal a specific DENV C interaction with VLDL, but not LDL. This binding is potassium-dependent and involves the DENV C N-terminal region, as previously observed for the DENV C-lipid droplets (LDs) interaction. A successful inhibition of DENV C-VLDL binding was achieved with a peptide drug lead. The similarities between LDs and VLDL, and between perilipin 3 (DENV C target on LDs) and ApoE, indicate ApoE as the molecular target on VLDL. We hypothesize that DENV may form lipoviroparticles, which would constitute a novel step on DENV life cycle.
  
  
  BACKGROUND
  Using atomic force microscopy-based force spectroscopy, dynamic light scattering, NMR, and computational analysis, these authors demonstrate that dengue viral capsid proteins (DENV C) bind to very low density lipoprotein surfaces, but not to LDLs, in a potassium-dependent manner. This observation suggests the formation of lipo-viroparticles, which may be a novel step in its life cycle, and may offer potential therapeutic interventions directed to this step.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: André F
authors.initials: AF
authors.lastname: Faustino
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Filomena A
authors.initials: FA
authors.lastname: Carvalho
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Ivo C
authors.initials: IC
authors.lastname: Martins
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Miguel A R B
authors.initials: MA
authors.lastname: Castanho
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Mohana-Borges
authors.affiliation: Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Centro Nacional de Ressonância Magnética Nuclear, Universidade Federal do Rio de Janeiro and National Institute of Structural Biology and Bioimage, Rio de Janeiro, Brazil.
authors.forename: Fábio C L
authors.initials: FC
authors.lastname: Almeida
authors.affiliation: Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Andrea T
authors.initials: AT
authors.lastname: Da Poian
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. Electronic address: nsantos@fm.ul.pt.
authors.forename: Nuno C
authors.initials: NC
authors.lastname: Santos
mesh_terms: D036022:Capsid Proteins / Q000378:metabolism*; D003715:Dengue / Q000235:genetics / Q000473:pathology / Q000821:virology*; D003716:Dengue Virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D011485:Protein Binding; D014771:Virion / Q000235:genetics / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D008079:Lipoproteins, VLDL; D011188:Potassium
keywords: AFM; AFM-based force spectroscopy; ApoE; Cα RMSD; D(H); DENV; DENV C; DLS; Dengue virus capsid protein; Dynamic light scattering; HCV; HSQC; LD; LDL; LDLR; LVP; Lipoproteins; NMR; Single-molecule studies; VLDL; apolipoprotein E; atomic force microscopy; dengue virus; dengue virus capsid protein; dynamic light scattering; hepatitis C virus; heteronuclear single quantum coherence; hydrodynamic diameter; lipid droplet; lipoviroparticles; low-density lipoprotein; low-density lipoprotein receptor; nuclear magnetic resonance; very low-density lipoprotein; α-carbons root mean squared deviation