Journal article
Biomechanical characterization of TIM protein-mediated Ebola virus-host cell adhesion
Scientific reports, Vol.9(1), pp.267-267
01/22/2019
DOI: 10.1038/s41598-018-36449-2
PMCID: PMC6342996
PMID: 30670766
Abstract
Since the most recent outbreak, the Ebola virus (EBOV) epidemic remains one of the world's public health and safety concerns. EBOV is a negative-sense RNA virus that can infect humans and non-human primates, and causes hemorrhagic fever. It has been proposed that the T-cell immunoglobulin and mucin domain (TIM) family proteins act as cell surface receptors for EBOV, and that the interaction between TIM and phosphatidylserine (PS) on the surface of EBOV mediates the EBOV-host cell attachment. Despite these initial findings, the biophysical properties of the TIM-EBOV interaction, such as the mechanical strength of the TIM-PS bond that allows the virus-cell interaction to resist external mechanical perturbations, have not yet been characterized. This study utilizes single-molecule force spectroscopy to quantify the specific interaction forces between TIM-1 or TIM-4 and the following binding partners: PS, EBOV virus-like particle, and EBOV glycoprotein/vesicular stomatitis virus pseudovirion. Depending on the loading rates, the unbinding forces between TIM and ligands ranged from 40 to 100 pN, suggesting that TIM-EBOV interactions are mechanically comparable to previously reported adhesion molecule-ligand interactions. The TIM-4-PS interaction is more resistant to mechanical force than the TIM-1-PS interaction. We have developed a simple model for virus-host cell interaction that is driven by its adhesion to cell surface receptors and resisted by membrane bending (or tension). Our model identifies critical dimensionless parameters representing the ratio of deformation and adhesion energies, showing how single-molecule adhesion measurements relate quantitatively to the mechanics of virus adhesion to the cell.
Details
- Title: Subtitle
- Biomechanical characterization of TIM protein-mediated Ebola virus-host cell adhesion
- Creators
- Matthew A. Dragovich - Lehigh UniversityNicole Fortoul - Lehigh UniversityAnand Jagota - Lehigh UniversityWei Zhang - Lehigh UniversityKrista Schutt - Lehigh UniversityYan Xu - Lehigh UniversityMichelle Sanabria - Lehigh UniversityDennis M. Moyer - Lehigh UniversitySven Moller-Tank - University of IowaWendy Maury - University of IowaX. Frank Zhang - Lehigh University
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.9(1), pp.267-267
- DOI
- 10.1038/s41598-018-36449-2
- PMID
- 30670766
- PMCID
- PMC6342996
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- R01AI077519; R15AI133634 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R15AI133634 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Lehigh University Lehigh Department of Bioengineering 1804117 / NSF; National Science Foundation (NSF)
- Language
- English
- Date published
- 01/22/2019
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297438202771
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