An international team of researchers has identified the human cells likely targeted by SARS-CoV-2, the coronavirus responsible for the Covid-19 pandemic. The cells are found in the lungs, nasal passages, and in the intestine, areas known for harboring the virus.
The study, published in the journal Cell, focused on two human proteins used by the virus to enter the cell. One is an enzyme called Type II transmembrane serine protease (TMPRSS2), which activate the spike protein used by the virus to enter the cell. The other is angiotensin-converting enzyme 2 (ACE2), where the viral “spike” protein binds so it can attach itself to the cell.
“As soon as we realized that the role of these proteins had been biochemically confirmed, we started looking to see where those genes were in our existing datasets,” senior author Jose Ordovas-Montanes, from the Boston Children Hospital, said in a statement. “We were really in a good position to start to investigate which are the cells that this virus might actually target.”
Most of the data come from labs that contribute to the Human Cell Atlas, whose ambitious goal is to catalog every gene activity of every cell in the human body. Thanks to this incredible repository, the team was able to locate where ACE2 and TMPRSS2 were active.
The researchers inspected the gene expression patterns for hundreds of different cells in the lungs, nasal passages, and in the intestine. Only a minority of cells express ACE2 and TMPRSS2. Those that do include goblet cells in the nasal passage (they secrete mucus) and type II pneumocytes found on the surface of the alveoli in the lungs. In the intestine, the cells that produce those proteins are called enterocytes, which help with the absorption of nutrients.
“This may not be the full story, but it definitely paints a much more precise picture than where the field stood before,” Ordovas-Montanes added. “Now we can say with some level of confidence that these receptors are expressed on these specific cells in these tissues.”
The work also found a peculiar link between ACE2 and interferon, a protein that is used by cells to fight off viral infections. When one is activated, so is the other. The findings suggest that SARS-CoV-2 might have uncovered a way to go around this natural defense using the activation of ACE2 to its advantage.
“This isn’t the only example of that,” Ordovas-Montanes said. “There are other examples of coronaviruses and other viruses that actually target interferon-stimulated genes as ways of getting into cells. In a way, it’s the most reliable response of the host.”
All the data from the study is freely available to use. The team hopes their findings can help in the search for a treatment for the disease.
