Identifying locations where the COVID-19 virus can enter human cells

Coronavirus 'map' identifies key virus entry points into the body.

Imperial scientists are working to create a map of the human body to understand better how coronavirus enter human cells.

Scientists have identified initial infection points for SARS-CoV-2 in the nose and eyes. Receptors were also found in the intestines and vital organs such as the heart.

Scientists found two specific cell types in the nose – called goblet and ciliated cells, as likely initial infection points for COVID-19. These cells have high levels of the entry proteins that the COVID-19 virus uses to get into our cells.

The SARS-CoV-2 coronavirus requires two essential proteins, called ACE2 and TMPRSS2, to enter human cells. The first is a receptor protein that the virus can dock to, while the second is a so-called protease that activates viral entry into the cell.

For the study, scientists analyzed genomic data from more than 20 different tissues of non-infected people. They also looked for which individual cells expressed both of two essential entry proteins that are used by the COVID-19 virus to infect our cells.

Dr. Michela Noseda, a senior study author from the National Heart and Lung Institute at Imperial, explained the study had revealed crucial insights – not only into how the virus gains access to the body, but also how the virus could target organs outside of the airways and leading to systemic disease. Heart tissue damage and consequent heart failure are observed in up to 20 percent of COVID-19 patients. Thus, it was crucial to investigate how the virus could enter heart cells, by mapping the location of the SARS-CoV-2 receptor in the heart, and the proteases that enable the virus to gain entry to cells.”

“We analyzed around 500,000 single cells from 14 human hearts and identified three types of cells that express the entry receptor: pericytes, which are found in the network of small blood vessels in the heart; cardiac muscle cells; and fibroblasts, the cells that help maintain the heart structure. Knowing the specific and likely target cells of the virus in the heart provides crucial information necessary to understand the mechanisms of damage and guide treatment choices.”

Dr. Waradon Sungnak, the first author on the paper from Wellcome Sanger Institute, said: “We found that the receptor protein – ACE2 – and the TMPRSS2 protease that can activate SARS-CoV-2 entry are expressed in cells in different organs, including the cells on the inner lining of the nose. We then revealed that mucus-producing goblet cells and ciliated cells in the nose had the highest levels of both these COVID-19 virus proteins, of all cells in the airways. This makes these cells the most likely initial infection route for the virus.”

“The two key entry proteins ACE2 and TMPRSS2 were also found in cells in the cornea of the eye and the lining of the intestine. This suggests another possible route of infection via the eye and tear ducts, and revealed a potential for fecal-oral transmission.”

Dr. Sarah Teichmann, a senior author from the Wellcome Sanger Institute and co-chair of the HCA Organising Committee, said: “As we’re building the Human Cell Atlas, it is already being used to understand COVID-19 and identify which of our cells are critical for initial infection and transmission. This information can be used to better understand how coronavirus spreads. Knowing which exact cell types are important for virus transmission also provides a basis for developing potential treatments to reduce the spread of the virus.”

The study was conducted in collaboration with the Wellcome Sanger Institute, University Medical Centre Groningen, University Cote d’Azur, and CNRS, Nice.

Journal Reference:
  1. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. DOI: 10.1038/s41591-020-0868-6

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