New coronavirus targets cells in the nose, lungs, and gut
28 April, 2020
A new study suggests that SARS-CoV-2, the virus that triggers COVID-19, is most probably to target specific cells within the nasal passages, lungs, and small intestine.
A fresh study by researchers from the Massachusetts Institute of Technology (MIT) and Harvard University, both in Cambridge, MA - alongside colleagues from other institutions - may have pinpointed the cells that SARS-CoV-2 generally targets in the body.
The analysis - the findings that will soon come in the journal Cell - built on existing investigations showing that SARS-CoV-2 uses two proteins that become receptors to invade host cells and replicate. These proteins are angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2).
The researchers wanted to discover which cells in the body express these proteins, and they centered on sets of cells in the nasal passages, lungs, and small intestine. This is because persons with COVID-19 frequently experience respiratory and digestive symptoms.
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“When we realized that the role of the proteins have been biochemically confirmed,” says study co-author Jose Ordovas-Montanes, Ph.D., “we started seeking to see where those genes were inside our existing datasets.”
“We were really in a good position to commence to investigate which are the cells that virus could actually target,” he adds.
“Our goal is to get information out to the city and also to share data when is humanly possible, in order that we can help accelerate ongoing efforts in the scientific and medical communities,” adds study co-author Prof. Alex Shalek, from MIT.
‘Painting a more precise picture’
The researchers used existing information to see their study and help them select the tissues that then they analyzed and experimented with.
“Because we've this incredible repository of information, we could actually begin to check out what would be likely target cells for infection,” says Prof. Shalek.
“Even though these datasets weren’t designed specifically to study [COVID-19], it’s hopefully given us a jump start identifying a number of the things that could be relevant there,” he continues.
Looking at cells from the nasal passages, lungs, and small intestine, the investigators were able to pinpoint the types of cell that SARS-CoV-2 probably “latches onto.”
The researchers found that in the nasal passages, “goblet secretory cells” - which produce mucus - express RNA which allows them to create both ACE2 and TMPRSS2. In lung tissue, they settled on type II pneumocytes, which will be the cells that line the alveoli (air sacs) and allow them to stay open.
Finally, in the tiny intestine, the team closed in on absorptive enterocytes, which are the cells that ensure the absorption of key nutrients.
“This might not exactly be the entire story, but it definitely paints a more precise picture than where in fact the field stood before. Now we are able to say with some degree of confidence that these receptors are expressed on these specific cells in these tissues.”
- Jose Ordovas-Montanes, Ph.D.
Questions about the role of interferon
During the course of their study, the researchers also discovered that the gene that encodes ACE2 may be linked to the activation of genes that also respond to interferon. This is a protein that helps trigger the immune response.
Following further experiments, the team discovered that interferon could activate the ACE2 gene in airway epithelial cells.
This unexpected finding led the researchers to assume that coronaviruses may have “learned” to carefully turn on proteins that are designed to help cells maintain their integrity against those very cells.
“This isn’t the only exemplory case of that,” notes Ordovas-Montanes. “There are other examples of coronaviruses and other viruses that truly target interferon-stimulated genes as ways of getting into cells. In ways, it’s the most dependable response of the host.”
Following on from their recent findings, the researchers are weighing the potential role of interferon with regards to infections with SARS-CoV-2.
On the one hand, they say, this protein may boost cells’ defenses against the virus. Alternatively, it's possible that interferon could also turn into a target for SARS-CoV-2.
“It’s hard to create any broad conclusions about the role of interferon from this virus,” Prof. Shalek explains.
“The only way we’ll begin to understand that's through carefully manipulated clinical trials,” he adds.
“What we want to do is put information out there, because there are so many rapid clinical responses that persons are making. We’re trying to create them alert to things that could be relevant,” Prof. Shalek concludes.
Source: www.medicalnewstoday.com
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