Neuroinvasion of SARS-CoV-2 in human and mouse brain.

The Journal of Experimental Medicine
Eric SongAkiko Iwasaki

Abstract

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.

References

Jan 16, 2007·PLoS Pathogens·Anjeanette RobertsKanta Subbarao
Nov 19, 2008·Journal of Neurochemistry·Huijing Xia, Eric Lazartigues
Sep 18, 2012·Cell Host & Microbe·Brian YordyAkiko Iwasaki
Sep 3, 2013·Nature·Madeline A LancasterJuergen A Knoblich
Sep 5, 2014·Nature Protocols·Madeline A Lancaster, Juergen A Knoblich
Apr 12, 2016·Science·Patricia P GarcezStevens K Rehen
May 31, 2016·Cell·Nicolas RenierMarc Tessier-Lavigne
Oct 26, 2018·Neuron·Neal D Amin, Sergiu P Paşca
Oct 9, 2019·Nature Methods·Bilal CakirIn-Hyun Park
Mar 23, 2020·Biochemical and Biophysical Research Communications·Furong QiZheng Zhang
Apr 25, 2020·Nature Medicine·Waradon SungnakUNKNOWN HCA Lung Biological Network
Apr 30, 2020·Infectious Diseases of Poverty·Meng-Yuan LiXiao-Sheng Wang
May 4, 2020·Trends in Neurosciences·Fernanda G De FeliceSergio T Ferreira
May 14, 2020·The New England Journal of Medicine·Victor G PuellesTobias B Huber
May 18, 2020·Cell·Daniel Blanco-MeloBenjamin R tenOever
Jun 3, 2020·Cell Host & Microbe·Shi-Hui SunYou-Chun Wang
Jun 6, 2020·Alzheimer's Research & Therapy·Michael T HenekaRobert Brown
Jun 13, 2020·Science·Laura PellegriniMadeline A Lancaster
Jun 13, 2020·The New England Journal of Medicine·Isaac H SolomonPardis Sabeti
Jun 18, 2020·Neurology·Tim CoolenXavier De Tiège
Jun 24, 2020·The Journal of Clinical Investigation·Hillary HosierHeather S Lipkind
Aug 5, 2020·The Journal of Experimental Medicine·Benjamin IsraelowAkiko Iwasaki
Sep 3, 2020·The EMBO Journal·Anand RamaniJay Gopalakrishnan
Oct 22, 2020·Science·Ludovico Cantuti-CastelvetriMikael Simons
Oct 22, 2020·Science·James L DalyYohei Yamauchi

❮ Previous
Next ❯

Citations

Feb 9, 2021·Brain Research·Valéry BielarzCharles Nicaise
Feb 5, 2021·Nature Metabolism·Janis A MüllerAlexander Kleger
Feb 27, 2021·Stem Cell Reports·Kristina DobrindtKristen J Brennand
Mar 6, 2021·Emerging Microbes & Infections·Kelvin Kai-Wang ToKwok-Yung Yuen
Feb 20, 2021·Biomedical Journal·Bruna A G de MeloMarimelia A Porcionatto
Feb 26, 2021·Stem Cell Reports·Anand RamaniJay Gopalakrishnan
Mar 21, 2021·Cell·Joachim L Schultze, Anna C Aschenbrenner
Apr 4, 2021·International Journal of Molecular Sciences·Michelle A EricksonWilliam A Banks
Apr 11, 2021·Nature Medicine·Liam GazianoUNKNOWN VA Million Veteran Program COVID-19 Science Initiative
Apr 20, 2021·Brain, Behavior, & Immunity Health·Larissa Daniele Bobermin, André Quincozes-Santos
May 1, 2021·International Journal of Molecular Sciences·Ghaydaa A ShehataHatem A Elshabrawy
May 1, 2021·Journal of Neurology·A L RenE J Needham
Apr 15, 2021·Current Opinion in Neurology·Shelli F FarhadianSerena Spudich
May 5, 2021·Veterinary Research·Bertrand PainMuriel Coulpier
May 5, 2021·Translational Neurodegeneration·Xiaohuan XiaJialin Zheng
May 7, 2021·Neuronal Signaling·Eilis Dowd, Declan P McKernan
May 9, 2021·Inflammation and Regeneration·Yoshitaka Kase, Hideyuki Okano
May 12, 2021·Journal of Neurology·Rebecca De LorenzoRoberto Furlan
May 11, 2021·Frontiers in Pharmacology·G KanimozhiN Rajendra Prasad
May 13, 2021·Multiple Sclerosis and Related Disorders·Mahdi BarzegarVahid Shaygannejad
Jun 3, 2021·Viruses·Belete A DesimmieKara S Willenburg
May 20, 2021·Nature·Eric Y WangAaron M Ring
Jun 4, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Rabia Bouali-Benazzouz, Abdelhamid Benazzouz
Jun 3, 2021·International Journal of Molecular Sciences·Joanna KulikowskaAlina Kułakowska
Jun 3, 2021·Journal of Clinical Medicine·Domenico NuzzoPasquale Picone
Jul 1, 2021·Trends in Biochemical Sciences·Ruchao PengGeorge Fu Gao
Jul 3, 2021·Nutrients·Hana M A FakhouryKhaled Alkattan
Jun 30, 2021·Stem Cell Research·Carolina da S G PedrosaMarília Zaluar P Guimarães
Jul 3, 2021·International Journal of Molecular Sciences·María Asunción Barreda-MansoRodrigo M Maza
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Huan CuiWenying Qiu
Jul 1, 2021·Intensive Care Medicine·M Elizabeth WilcoxDaniel F McAuley

❮ Previous
Next ❯

Datasets Mentioned

BETA
GTX632604

Methods Mentioned

BETA
RNA-seq
Electron microscopy
single cell sequencing
single-cell sequencing
ELISA
light sheet microscopy
PCR
fluorescence microscopy
Assay
ELISAs

Related Concepts

Related Feeds

3D Cellular Models of Brain and Neurodegeneration

Brain organoids are three-dimensional in vitro cellular models of the brain that can recapitulate many processes such as the neurodevelopment. In addition, these organoids can be combined with other cell types, such as neurons and astrocytes to study their interactions in assembloids. Disease processes can also be modeled by induced pluripotent stem cell-derived organoids and assembloids from patients with neurodegenerative disorders. Discover the latest research on the models here.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Brain Organoids in Disease Modeling

Brain organoids are three-dimensional cell culture models derived from human pluripotent stem cells. Since they resemble the embryonic brain, they can be used to help study brain biology, early brain development, and brain diseases. Discover the latest research on brain organoids in disease modeling here.