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ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response
ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe COVID-19. However, it is unclear whether ApoE4 alters COVID-19 susceptibility or severity, and the role of direct viral infection in brain cells remains obscure. We tested the neurotropism o...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832490/ https://www.ncbi.nlm.nih.gov/pubmed/33450186 http://dx.doi.org/10.1016/j.stem.2020.12.018 |
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author | Wang, Cheng Zhang, Mingzi Garcia, Gustavo Tian, E. Cui, Qi Chen, Xianwei Sun, Guihua Wang, Jinhui Arumugaswami, Vaithilingaraja Shi, Yanhong |
author_facet | Wang, Cheng Zhang, Mingzi Garcia, Gustavo Tian, E. Cui, Qi Chen, Xianwei Sun, Guihua Wang, Jinhui Arumugaswami, Vaithilingaraja Shi, Yanhong |
author_sort | Wang, Cheng |
collection | PubMed |
description | ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe COVID-19. However, it is unclear whether ApoE4 alters COVID-19 susceptibility or severity, and the role of direct viral infection in brain cells remains obscure. We tested the neurotropism of SARS-CoV2 in human-induced pluripotent stem cell (hiPSC) models and observed low-grade infection of neurons and astrocytes that is boosted in neuron-astrocyte co-cultures and organoids. We then generated isogenic ApoE3/3 and ApoE4/4 hiPSCs and found an increased rate of SARS-CoV-2 infection in ApoE4/4 neurons and astrocytes. ApoE4 astrocytes exhibited enlarged size and elevated nuclear fragmentation upon SARS-CoV-2 infection. Finally, we show that remdesivir treatment inhibits SARS-CoV2 infection of hiPSC neurons and astrocytes. These findings suggest that ApoE4 may play a causal role in COVID-19 severity. Understanding how risk factors impact COVID-19 susceptibility and severity will help us understand the potential long-term effects in different patient populations. |
format | Online Article Text |
id | pubmed-7832490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78324902021-01-26 ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response Wang, Cheng Zhang, Mingzi Garcia, Gustavo Tian, E. Cui, Qi Chen, Xianwei Sun, Guihua Wang, Jinhui Arumugaswami, Vaithilingaraja Shi, Yanhong Cell Stem Cell Short Article ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe COVID-19. However, it is unclear whether ApoE4 alters COVID-19 susceptibility or severity, and the role of direct viral infection in brain cells remains obscure. We tested the neurotropism of SARS-CoV2 in human-induced pluripotent stem cell (hiPSC) models and observed low-grade infection of neurons and astrocytes that is boosted in neuron-astrocyte co-cultures and organoids. We then generated isogenic ApoE3/3 and ApoE4/4 hiPSCs and found an increased rate of SARS-CoV-2 infection in ApoE4/4 neurons and astrocytes. ApoE4 astrocytes exhibited enlarged size and elevated nuclear fragmentation upon SARS-CoV-2 infection. Finally, we show that remdesivir treatment inhibits SARS-CoV2 infection of hiPSC neurons and astrocytes. These findings suggest that ApoE4 may play a causal role in COVID-19 severity. Understanding how risk factors impact COVID-19 susceptibility and severity will help us understand the potential long-term effects in different patient populations. Elsevier Inc. 2021-02-04 2021-01-04 /pmc/articles/PMC7832490/ /pubmed/33450186 http://dx.doi.org/10.1016/j.stem.2020.12.018 Text en © 2020 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Short Article Wang, Cheng Zhang, Mingzi Garcia, Gustavo Tian, E. Cui, Qi Chen, Xianwei Sun, Guihua Wang, Jinhui Arumugaswami, Vaithilingaraja Shi, Yanhong ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response |
title | ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response |
title_full | ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response |
title_fullStr | ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response |
title_full_unstemmed | ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response |
title_short | ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response |
title_sort | apoe-isoform-dependent sars-cov-2 neurotropism and cellular response |
topic | Short Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832490/ https://www.ncbi.nlm.nih.gov/pubmed/33450186 http://dx.doi.org/10.1016/j.stem.2020.12.018 |
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