The 3D assembly shows how SARS-CoV-2 infects brain cells

Researchers at the University of California San Diego School of Medicine and the Rady Children’s Institute of Genomic Medicine have produced a stem cell model that demonstrates a potential route of entry for SARS-CoV-2, the virus which causes COVID-19, in the human brain.

The findings are published in the online issue of July 9, 2021 Nature medicine.

“Clinical and epidemiological observations suggest that the brain may be involved in SARS-CoV-2 infection,” said lead author Joseph Gleeson, MD, Rady’s professor of neuroscience at UC San School of Medicine Diego and director of neuroscience research at the Rady Children’s Institute for Genomic Medicine.

“The COVID19 perspective induced brain damage has become one of the main concerns in cases of “long COVID,” but human culture neurons are not susceptible to infection. Previous publications suggest that cells that make spinal fluid could be infected with SARS-CoV-2, but other routes of entry seemed likely. “

Gleeson and colleagues, who included neuroscientists and infectious disease specialists, confirmed that human neuronal cells are resistant to SARS-CoV-2 infection. However, recent studies have suggested that other types of brain cells could serve as “Trojan horses.”

Pericytes are specialized cells that surround blood vessels and carry the SARS-CoV2 receptor. The researchers introduced pericytes into cultures of three-dimensional neuronal cells (brain organoids) to create “assembloids,” a more sophisticated stem cell model in the human body. These assoids contained many types of brain cells, in addition to pericytes, and had a robust SARS-CoV-2 infection.

The coronavirus was able to infect pericytes, which served as localized factories for the production of SARS-CoV-2. These locally produced SARS-CoV-2s could spread to other cell types, causing widespread damage. With this improved modeling system, they found that the support cells known as astrocytes were the primary target of this secondary infection.

The results, according to Gleeson, indicate that a potential route of SARS-CoV-2 to the brain is through blood vessels, where SARS-CoV-2 can infect pericytes, and then SARS-CoV-2 is infected. it can spread to other types of brains. cells.

“Alternatively, infected pericytes could cause inflammation of blood vessels, followed by clotting, stroke, or bleeding, complications seen in many patients with SARS-CoV-2 hospitalized in intensive care units.”

Researchers now plan to focus on developing improved assembloids that contain not only pericytes, but also blood vessels able to pump blood to better model the intact human brain. Through these models, Gleeson said, greater insight into infectious and other diseases human brain a disease could emerge.