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Label-Free Digital Holo-tomographic Microscopy Reveals Virus-Induced Cytopathic Effects in Live Cells

Yakimovich, A; Witte, R; Andriasyan, V; Georgi, F; Greber, UF; (2018) Label-Free Digital Holo-tomographic Microscopy Reveals Virus-Induced Cytopathic Effects in Live Cells. mSphere , 3 (6) , Article e00599. 10.1128/mSphereDirect.00599-18. Green open access

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Abstract

Cytopathic effects (CPEs) are a hallmark of infections. CPEs are difficult to observe due to phototoxicity from classical light microscopy. We report distinct patterns of virus infections in live cells using digital holo-tomographic microscopy (DHTM). DHTM is label-free and records the phase shift of low-energy light passing through the specimen on a transparent surface with minimal perturbation. DHTM measures the refractive index (RI) and computes the refractive index gradient (RIG), unveiling optical heterogeneity in cells. We find that vaccinia virus (VACV), herpes simplex virus (HSV), and rhinovirus (RV) infections progressively and distinctly increased RIG. VACV infection, but not HSV and RV infections, induced oscillations of cell volume, while all three viruses altered cytoplasmic membrane dynamics and induced apoptotic features akin to those caused by the chemical compound staurosporine. In sum, we introduce DHTM for quantitative label-free microscopy in infection research and uncover virus type-specific changes and CPE in living cells with minimal interference. // IMPORTANCE This study introduces label-free digital holo-tomographic microscopy (DHTM) and refractive index gradient (RIG) measurements of live, virus-infected cells. We use DHTM to describe virus type-specific cytopathic effects, including cyclic volume changes of vaccinia virus infections, and cytoplasmic condensations in herpesvirus and rhinovirus infections, distinct from apoptotic cells. This work shows for the first time that DHTM is suitable to observe virus-infected cells and distinguishes virus type-specific signatures under noninvasive conditions. It provides a basis for future studies, where correlative fluorescence microscopy of cell and virus structures annotate distinct RIG values derived from DHTM.

Type: Article
Title: Label-Free Digital Holo-tomographic Microscopy Reveals Virus-Induced Cytopathic Effects in Live Cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/mSphereDirect.00599-18
Publisher version: https://doi.org/10.1128/mSphereDirect.00599-18
Language: English
Additional information: Copyright © 2018 Yakimovich et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Keywords: Actin, Adenovirus, Apoptosis, Cell Contraction, Cell Volume, Cytopathogenic Effect, Viral, Dynamics, Hela Cells, Herpes Simplex Virus, Holographic Microscopy, Humans, Inhibition, Label-free microscopy, Macropinocytosis, Membrane Blebbing, Microbiology, Microscopy, Protein, Refractive Index, Replication, Rhinovirus, Tomography, Vaccinia Virus, Virus Infection
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10078130
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