Neuroinvasion of SARS-CoV-2 in human and mouse brain
| Autor: | Aaron M. Ring, Akiko Iwasaki, Stéphane Haïk, Kai Zhang, Murat Gunel, Etienne Levavasseur, Alice Lu-Culligan, Yuki Yasumoto, Alba Sprado, Mia Madel Alfajaro, Shelli F. Farhadian, Tamas L. Horvath, Angeliki Louvi, Evelyn Ng, Orr-El Weizman, Syed Kazmi, Guilin Wang, John Wheeler, Jean-Leon Thomas, Craig B. Wilen, Shrikant Mane, Klara Szigeti-Buck, Nicolas Renier, Christopher Castaldi, Eric Song, Feimei Liu, Jaime Heltke, Yile Dai, Kaya Bilguvar, Benjamin Fontes, Neal G. Ravindra, Benjamin Israelow, Danielle Seilhean, Anita Huttner, Isabelle Plu, Ce Zhang, Peiwen Lu, David van Dijk, Sophie Skriabine |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Antagonists & inhibitors Central nervous system Immunology Virus Article Infectious Disease and Host Defense Mice 03 medical and health sciences 0302 clinical medicine Immune system Cerebrospinal fluid In vivo Interferon Organoid Animals Humans Medicine Immunology and Allergy Antibodies Blocking skin and connective tissue diseases 030304 developmental biology Cerebral Cortex Neurons 0303 health sciences biology SARS-CoV-2 business.industry Respiratory disease fungi Respiratory infection COVID-19 Human brain Middle Aged medicine.disease 3. Good health Organoids Disease Models Animal 030104 developmental biology medicine.anatomical_structure biology.protein Female Angiotensin-Converting Enzyme 2 Antibody business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Experimental Medicine The Journal of Experimental Medicine bioRxiv article-version (status) pre article-version (number) 2 |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20202135 |
| Popis: | Neurological symptoms are frequently observed in COVID-19. Here, we examine the neuroinvasive potential of SARS-CoV-2 and demonstrate infection of neurons in three separate approaches: mouse model, human brain organoid, and autopsy of COVID-19 patients. Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2. Graphical Abstract |
| Databáze: | OpenAIRE |
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