By Michael Le Page

A team in the Netherlands has managed to capture 3D images of human airway cells infected by SARS-CoV-2 using an extraordinary microscopic technique. The images show how the coronavirus alters the structure of the cells it infects, and might help drug development.
Researchers at Utrecht University grew cells taken from the noses of healthy volunteers and infected some of the cells with the coronavirus. They then stained the cells with fluorescent dyes that bind to fatty membranes (the blue parts at the start of the video above), proteins (the magenta parts at the start of the video) and the spike protein of the coronavirus (the purple dots appearing from 0:17 onwards).
Next, the cells were cut up by enzymes and embedded in a gel. When water is added to the gel, it swells, enlarging the embedded structures. The technique (called expansion microscopy) was developed by other groups, but these researchers improved on it, enabling them to enlarge samples tenfold in each dimension.
This means optical microscopes can effectively view structures just 20 nanometres wide – including the SARS-CoV-2 virus, which is around 100 nanometres in diameter – whereas normally they can’t properly view objects smaller than 200 nanometres across.
The resulting images show that large membrane-bound structures involved in virus formation appear inside infected airway cells. By staining a specific protein, the team identified these structures as so-called multivesicular bodies that have grown abnormally large. They have also been seen in electron microscope images of cells infected by SARS-CoV-2, but their identity wasn’t clear.

The surfaces of human airway cells are covered in two kinds of hair-like structures. The larger ones, called cilia, beat to move mucus along the airways and keep them clear of dust. Then there are the smaller microvilli that increase cells’ surface area to help with absorption.
The microvilli in infected cells become longer and sometimes branched. In the video, pink dots reveal the presence of spike proteins along them, often right at the tips. This suggests that new viruses bud off the tips of the microvilli in airway cells, which is known to happen with some other viruses, such as influenza viruses.
The images also show that covid-19 infection damages the cilia, which are clustered and misshapen in infected cells. It isn’t clear why, as there are no spike proteins on them.
The team also infected cells originally taken from monkey kidneys. These cells usually have a smooth surface, but infected cells had numerous protrusions called filopodia from which viruses appear to bud. The team thinks the process that causes filopodia to form is the same as the one that makes microvilli longer in airway cells.
New Scientist contacted the researchers, but they didn’t want to talk about their findings until they are published in a peer-reviewed journal.
Reference: bioXriv, DOI: 10.1101/2021.08.05.455126
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