scholarly journals Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1004 ◽  
Author(s):  
Sang Ah Yi ◽  
Ki Hong Nam ◽  
Jihye Yun ◽  
Dongmin Gim ◽  
Daeho Joe ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Cell Receptor ◽  
Host Cell Receptor ◽  
Viral Particles ◽  
Mature Neurons ◽  
Multiple Symptoms ◽  
The Brain ◽  
Neurological Infection

Since the global outbreak of SARS-CoV-2 (COVID-19), infections of diverse human organs along with multiple symptoms continue to be reported. However, the susceptibility of the brain to SARS-CoV-2, and the mechanisms underlying neurological infection are still elusive. Here, we utilized human embryonic stem cell-derived brain organoids and monolayer cortical neurons to investigate infection of brain with pseudotyped SARS-CoV-2 viral particles. Spike-containing SARS-CoV-2 pseudovirus infected neural layers within brain organoids. The expression of ACE2, a host cell receptor for SARS-CoV-2, was sustained during the development of brain organoids, especially in the somas of mature neurons, while remaining rare in neural stem cells. However, pseudotyped SARS-CoV-2 was observed in the axon of neurons, which lack ACE2. Neural infectivity of SARS-CoV-2 pseudovirus did not increase in proportion to viral load, but only 10% of neurons were infected. Our findings demonstrate that brain organoids provide a useful model for investigating SARS-CoV-2 entry into the human brain and elucidating the susceptibility of the brain to SARS-CoV-2.

scholarly journals Ethanol Upregulates NMDA Receptor Subunit Gene Expression in Human Embryonic Stem Cell-Derived Cortical Neurons

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0134907 ◽  
Author(s):  
Yangfei Xiang ◽  
Kun-Yong Kim ◽  
Joel Gelernter ◽  
In-Hyun Park ◽  
Huiping Zhang
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Nmda Receptor ◽  
Embryonic Stem Cell ◽  
Cortical Neurons ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Receptor Subunit ◽  
Subunit Gene ◽  
Nmda Receptor Subunit

scholarly journals Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitors Remyelinate the Brain and Rescue Behavioral Deficits following Radiation

2015 ◽  
Vol 16 (2) ◽  
pp. 198-210 ◽  
Author(s):  
Jinghua Piao ◽  
Tamara Major ◽  
Gordon Auyeung ◽  
Edelweiss Policarpio ◽  
Jayanthi Menon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Behavioral Deficits ◽  
Oligodendrocyte Progenitors ◽  
The Brain

scholarly journals Both Spike and Background Genes Contribute to Murine Coronavirus Neurovirulence

2006 ◽  
Vol 80 (14) ◽  
pp. 6834-6843 ◽  
Author(s):  
Kathryn T. Iacono ◽  
Lubna Kazi ◽  
Susan R. Weiss
Keyword(s):  
Immune Response ◽  
Hepatitis Virus ◽  
Cell Receptor ◽  
Innate Immune ◽  
Cell Immune Response ◽  
Spike Gene ◽  
Recombinant Viruses ◽  
Host Cell Receptor ◽  
Viral Genes ◽  
The Brain

ABSTRACT Various strains of mouse hepatitis virus (MHV) exhibit different pathogenic phenotypes. Infection with the A59 strain of MHV induces both encephalitis and hepatitis, while the highly neurovirulent JHM strain induces a fatal encephalitis with little, if any, hepatitis. The pathogenic phenotype for each strain is determined by the genetic composition of the viral genome, as well as the host immune response. Using isogenic recombinant viruses with A59 background genes differing only in the spike gene, we have previously shown that high neurovirulence is associated with the JHM spike protein, the protein responsible for attachment to the host cell receptor (J. J. Phillips, M. M. Chua, G. F. Rall, and S. R. Weiss, Virology 301:109-120, 2002). Using another set of isogenic recombinant viruses with JHM background genes expressing either the JHM or A59 spike, we have further investigated the roles of viral genes in pathogenesis. Here, we demonstrate that the high neurovirulence of JHM is associated with accelerated spread through the brain and a heightened innate immune response that is characterized by high numbers of infiltrating neutrophils and macrophages, suggesting an immunopathogenic component to neurovirulence. While expression of the JHM spike is sufficient to confer a neurovirulent phenotype, as well as increased macrophage infiltration, background genes contribute to virulence as well, at least in part, by dictating the extent of the T-cell immune response.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2

2008 ◽  
Vol 82 (15) ◽  
pp. 7264-7275 ◽  
Author(s):  
Jason Netland ◽  
David K. Meyerholz ◽  
Steven Moore ◽  
Martin Cassell ◽  
Stanley Perlman
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Cell Receptor ◽  
Neurological Sequelae ◽  
Angiotensin Converting Enzyme 2 ◽  
Brain Infection ◽  
Host Cell Receptor ◽  
Coronavirus Infection ◽  
The Brain ◽  
Major Target

ABSTRACT Infection of humans with the severe acute respiratory syndrome coronavirus (SARS-CoV) results in substantial morbidity and mortality, with death resulting primarily from respiratory failure. While the lungs are the major site of infection, the brain is also infected in some patients. Brain infection may result in long-term neurological sequelae, but little is known about the pathogenesis of SARS-CoV in this organ. We previously showed that the brain was a major target organ for infection in mice that are transgenic for the SARS-CoV receptor (human angiotensin-converting enzyme 2). Herein, we use these mice to show that virus enters the brain primarily via the olfactory bulb, and infection results in rapid, transneuronal spread to connected areas of the brain. This extensive neuronal infection is the main cause of death because intracranial inoculation with low doses of virus results in a uniformly lethal disease even though little infection is detected in the lungs. Death of the animal likely results from dysfunction and/or death of infected neurons, especially those located in cardiorespiratory centers in the medulla. Remarkably, the virus induces minimal cellular infiltration in the brain. Our results show that neurons are a highly susceptible target for SARS-CoV and that only the absence of the host cell receptor prevents severe murine brain disease.

scholarly journals Graphene foam as a biocompatible scaffold for culturing human neurons

2018 ◽  
Vol 5 (3) ◽  
pp. 171364 ◽  
Author(s):  
Giovanna M. D'Abaco ◽  
Cristiana Mattei ◽  
Babak Nasr ◽  
Emma J. Hudson ◽  
Abdullah J. Alshawaf ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Supporting Cell ◽  
Neuronal Maturation ◽  
Graphene Foam ◽  
Neuronal Tissue ◽  
Human Neurons ◽  
Circuit Formation ◽  
Maturation Function

In this study, we explore the use of electrically active graphene foam as a scaffold for the culture of human-derived neurons. Human embryonic stem cell (hESC)-derived cortical neurons fated as either glutamatergic or GABAergic neuronal phenotypes were cultured on graphene foam. We show that graphene foam is biocompatible for the culture of human neurons, capable of supporting cell viability and differentiation of hESC-derived cortical neurons. Based on the findings, we propose that graphene foam represents a suitable scaffold for engineering neuronal tissue and warrants further investigation as a model for understanding neuronal maturation, function and circuit formation.

COVID 19 – Eye Issues

2020 ◽  
Vol 5 (Special) ◽  
Keyword(s):  
Host Cell ◽  
Target Cell ◽  
Cell Receptor ◽  
Human Tissues ◽  
Type Ii ◽  
Cell Infection ◽  
Host Cell Receptor ◽  
Infected Cells ◽  
Cellular Entry

The coronavirus illness (COVID-19) is caused by a new recombinant SARS-CoV (SARS-CoV) virus (SARS-CoV-2). Target cell infection by SARS-CoV is mediated by the prickly protein of the coronavirus and host cell receptor, enzyme 2 converting angiotensin (ACE2) [3]. Similarly, a recent study suggests that cellular entry by SARS-CoV-2 is dependent on both ACE2 as well as type II transmembrane axial protease (TMPRSS2) [4]. This means that detection of ACE2 and PRSS2 expression in human tissues can predict potential infected cells and their respective effects in COVID-19 patients [1].

IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche

2020 ◽  
Author(s):  
Wamaitha SE ◽  
Grybel KJ ◽  
Alanis-Lobato G ◽  
Gerri C ◽  
Ogushi S ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Self Renewal
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