Research: how coronavirus uses the body’s normal defenses to infect

A study by scientists from the Boston Children’s Hospital and the Massachusetts Institute of Technology, names the types of cells that are likely to be affected by the new coronavirus. But at the same time, the results unexpectedly showed that one of the main defense systems of our body can actually help the virus infect these very cells.

When news of the outbreak of coronavirus in China appeared, the authors of the latest study, Ph.D. Jose Ordovas-Montanes and Alex K. Shalek, already studied various types of cells from the human respiratory system and intestines. They also collected data from primates and mice.

And in February, they began to delve into this information – they began to study cells from tissues such as the mucous membrane of the nasal cavity, lungs and intestines, based on the reported symptoms and the location of the virus.

Recent studies have shown that SARS-CoV-2, similar to the other SARS-CoV coronavirus that caused the SARS pandemic in 2002-2003, uses the ACE2 receptor to penetrate human cells, aided by the TMPRSS2 enzyme. This prompted researchers to ask a simple question: which cells of the respiratory and intestinal tissue express both ACE2 and TMPRSS2?

To find the answer, the team turned to RNA sequencing of individual cells. She found that only a tiny percentage of cells from the human respiratory and intestinal organs, often well below 10%, produce both ACE2 and TMPRSS2. These cells are divided into three types: goblet cells in the nose that secrete mucus; lung cells, known as type 2 pneumocytes, which are necessary for the normal functioning of the alveoli; and one type of so-called enterocytes, which line the small intestine and are involved in the absorption of nutrients.

Sampling from non-human primates showed a similar pattern of virus susceptible cells. These data will help to understand why these cells are important for the life cycle of the virus, which will allow for more effective research to find a cure.

But the second conclusion of the study was even more interesting. Scientists have found that ACE2, which plays an important role in the penetration of a new coronavirus into human cells, is stimulated by interferon – not a drug, but a protein that is secreted by the body’s cells in response to virus invasion. Interferon actually includes ACE2 at higher levels, potentially giving the virus new pathways for entry.

That is, although ACE2 is usually designed to protect, the new coronavirus uses this enzyme as a target. So scientists suggest that the virus uses this normal protective reaction of the body in its life cycle.

Researchers also emphasized that it is too early to try to link the results of the study with the “cytokine storm,” an adverse inflammatory reaction reported in many sick patients with COVID-19. Cytokines are a family of chemicals that combine the body’s immune responses to fight infections, and interferon is part of this “family.” As the authors of the work note, “perhaps we are witnessing a cytokine storm due to the inability of interferon to limit the virus from the very beginning, so the lungs begin to“ call for help ”. This is exactly what we are trying to understand right now. ”

The team also wants to study what the virus does in the cells that it targets, and to examine tissue samples from children and adults to understand why COVID-19 usually occurs in young people in a milder form.