April 3, 2023
Keio University School of Medicine
Fujita Health University School of Medicine
Project Lecturer Yoshitaka Kase (Lecturer, Department of Clinical Regenerative Medicine, Fujita Health University School of Medicine) and Professor Hideyuki Okano of the Department of Physiology, Keio University School of Medicine, have discovered that SARS-CoV-2 infects microglia in the brain.
In COVID-19, which causes central nervous system disorders, the question of whether SARS-CoV-2 can directly infect nerve cells (neurons) has been addressed by numerous studies worldwide, which have shown that SARS-CoV-2 has difficulty infecting neurons. However, changes in infectivity when the virus mutates and its infectivity to other types of cells that make up the brain had not been sufficiently verified. Furthermore, if it is difficult for the virus to infect neurons, it was not clear why central nervous system disorders occur, and systemic inflammation was thought to be the cause.
Therefore, this research group generated neurons, astrocytes, and microglia, the main constituent cells of the brain, as well as brain organoids from human iPS cells to investigate the virus's infectivity. The results showed that from the initial Alpha variant to the Delta and Omicron variants, SARS-CoV-2 efficiently infects microglia, while it does not infect neurons or neural stem cells. Additionally, while SARS-CoV-2 infects cells via cellular receptors, it was found that DPP4, rather than ACE2, which is generally considered the receptor for SARS-CoV-2, is a strong candidate for this infection of microglia.
Although many reports worldwide have indicated that SARS-CoV-2 cannot infect neurons, the results regarding the analysis of variants and infection of human microglia are new findings. These results suggest that central nervous system disorders caused by COVID-19 may not be due to direct viral infection of neurons, but rather that the key may be the abnormal activation of the immune system caused by infection of microglia.
The results of this research are scheduled to be published in a special issue of Experimental Neurology , and the online version was released in advance on March 11 (Coordinated Universal Time).
Please see below for the full press release.