Nanomedicine. 2014 Jan;10(1):247-55. doi: 10.1016/j.nano.2013.06.004. Epub 2013 Jun 20.
Dengue virus capsid protein interacts specifically with very low-density lipoproteins.
Faustino AF1, Carvalho FA1, Martins IC1, Castanho MA1, Mohana-Borges R2, Almeida FC3, Da Poian AT4, Santos NC5.
Tiivistelmä, 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.
FROM THE CLINICAL EDITOR:
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.
© 2013.
FROM THE CLINICAL EDITOR:
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.
© 2013.
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
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
- PMID:
- 23792329
- [PubMed - indexed for MEDLINE]
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