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fredag 14 november 2014

Vaipattoman Dengue-viruksen (DENV) kohdemolekyyli on VLDL. ApoE on VLDL kohde.

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.

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.

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.
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
[PubMed - indexed for MEDLINE]

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