Highly Sensitive, Engineered Magnetic Nanosensors to Investigate the Ambiguous Activity of Zika Virus and Binding Receptors

Sci Rep. 2017 Aug 7;7(1):7377. doi: 10.1038/s41598-017-07620-y.

Abstract

The aim of this research is twofold: 1) to shed light on zika's binding and entry mechanism while 2) demonstrating the effectiveness of our magnetic relaxation platform to achieve this goal. Magnetic relaxation-sensitive nanoparticles (MRNPs) are used in a novel fashion to analyze binding interactions between the zika envelope protein (ZENV) and proposed host cell receptors: AXL, HSP70, and TIM-1. Computational analysis is also utilized to examine these binding interactions for the first time. In addition, the role of crizotinib as a potential binding inhibitor is demonstrated and the possibility of ligand-independent phosphatidylserine-mediated binding is explored. Our findings suggest that while the extracellular domain of AXL has the highest affinity for ZENV; HSP70, TIM-1, and phosphatidylserine might also play active roles in zika tropism, which offers a potential explanation for the variety of zika-associated symptoms. This is, to our knowledge, the first time that MRNPs have been used to examine and quantify host-zika interactions. Our magnetic relaxation platform allows for timely and sensitive analysis of these intricate binding relationships, and it is easily customizable for further examination of additional host-pathogen interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axl Receptor Tyrosine Kinase
  • Biosensing Techniques* / methods
  • Crizotinib / chemistry
  • Crizotinib / metabolism
  • Ferric Compounds / chemistry
  • Host-Pathogen Interactions*
  • Humans
  • Hydrogen-Ion Concentration
  • Magnetite Nanoparticles / chemistry
  • Models, Biological
  • Models, Molecular
  • Nanotechnology*
  • Organ Specificity
  • Phosphatidylserines / chemistry
  • Phosphatidylserines / metabolism
  • Protein Conformation
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Virus / chemistry
  • Receptors, Virus / metabolism*
  • Temperature
  • Virus Attachment
  • Zika Virus / physiology*
  • Zika Virus Infection / metabolism*
  • Zika Virus Infection / virology*

Substances

  • Ferric Compounds
  • Magnetite Nanoparticles
  • Phosphatidylserines
  • Proto-Oncogene Proteins
  • Receptors, Virus
  • ferric oxide
  • Crizotinib
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase