4.6 Review

Human Brain Organoids as Models for Central Nervous System Viral Infection

Related references

Note: Only part of the references are listed.
Review Clinical Neurology

Unravelling Pathophysiology of Neurological and Psychiatric Complications of COVID-19 Using Brain Organoids

Jing-Han Ng et al.

Summary: Brain organoid models derived from human pluripotent stem cells provide valuable insights into the neurotropic properties of SARS-CoV-2. While neurons can be infected by SARS-CoV-2, the extent of neurotropism is limited compared to the high susceptibility of choroidal epithelial cells. These studies also shed light on the mechanisms of cellular entry, viral replication, and downstream effects of SARS-CoV-2 infection. The neuropsychiatric manifestations of COVID-19 may be a result of both direct neuronal invasion and indirect consequences of neuroinflammation.

NEUROSCIENTIST (2023)

Review Immunology

Human Brain Organoids as an In Vitro Model System of Viral Infectious Diseases

Xuan Su et al.

Summary: Brain organoids, or brainoids, have shown great potential in studying central nervous system infections. They can be used to model Zika virus infection and uncover the relationship between Zika virus infection and microcephaly. Brain organoids have been utilized in investigating the pathogenesis of various viral infections of the CNS and aiding in the development of new drugs. However, there are limitations that need to be addressed and further research is required to improve their application.

FRONTIERS IN IMMUNOLOGY (2022)

Review Biochemistry & Molecular Biology

Applications of Brain Organoids for Infectious Diseases

Wenqiang Fan et al.

Summary: This article introduces the definition, characteristics, and applications of brain organoids, with a focus on their application in the study of neurotropic viral infections.

JOURNAL OF MOLECULAR BIOLOGY (2022)

Article Neurosciences

A human-derived 3D brain organoid model to study JC virus infection

Paula Barreras et al.

Summary: This study developed a human brain organoid model of JC virus (JCV) infection, which successfully simulated the pathogenesis of PML. The results showed that JCV infection mainly occurred in oligodendrocytes and astrocytes, while no evidence of neuronal infection was found. This model provides a valuable tool for studying the mechanisms of JCV infection and the pathogenesis of PML, as well as exploring potential therapeutic approaches.

JOURNAL OF NEUROVIROLOGY (2022)

Article Cell & Tissue Engineering

Tel:+82-2-880-1298, Fax:+82-2-876-7610

Myung Geun Kook et al.

Summary: This study developed vascularized cerebral organoids through the assembly of brain organoids with vascular spheroids, providing a model for studying human cortical development and an opportunity to explore neurological diseases.

INTERNATIONAL JOURNAL OF STEM CELLS (2022)

Review Pediatrics

Update on Viral Infections Involving the Central Nervous System in Pediatric Patients

Giovanni Autore et al.

Summary: Infections of the central nervous system in children are mainly caused by viruses and can be life-threatening. Prompt lumbar puncture and polymerase chain reaction analysis of cerebrospinal fluid are recommended for suspected cases. Treatment for viral CNS infections relies on supportive care, with empiric therapy against herpes simplex virus being started early.

CHILDREN-BASEL (2021)

Article Cell & Tissue Engineering

ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response

Cheng Wang et al.

Summary: The study suggests a potential causal role of ApoE4 in the severity of COVID-19, as tested in human-induced pluripotent stem cell (hiPSC) models for SARS-CoV-2 neurotropism. Increased infection rates of SARS-CoV-2 in ApoE4/4 neurons and astrocytes were observed, with changes in ApoE4 astrocytes upon infection. Remdesivir treatment was effective in inhibiting SARS-CoV2 infection in hiPSC neurons and astrocytes, highlighting the impact of risk factors on COVID-19 severity.

CELL STEM CELL (2021)

Article Immunology

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

Eric Song et al.

Summary: The study showed through three approaches that SARS-CoV-2 is capable of infecting brain neurons, leading to metabolic changes and pathological features without triggering type I interferon responses. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and the unexpected consequence of direct infection of neurons by the virus.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

Article Virology

Modeling Aβ42 Accumulation in Response to Herpes Simplex Virus 1 Infection: Two Dimensional or Three Dimensional?

Eric E. Abrahamson et al.

Summary: The study suggests that HSV-1 infection in the brain may lead to the accumulation of A beta 42, thus contributing to the onset of Alzheimer's disease. Additionally, by comparing 2D and 3D neuronal cultures, different patterns of accumulation were observed, emphasizing the importance of 3D cultures in modeling host-pathogen interactions.

JOURNAL OF VIROLOGY (2021)

Article Virology

Broadly Active Antiviral Compounds Disturb Zika Virus Progeny Release Rescuing Virus-Induced Toxicity in Brain Organoids

Aleksandra Pettke et al.

Summary: This study demonstrates the potential therapeutic window of novel antiviral compounds against ZIKV in infected brain cells, rescuing ZIKV-induced neurotoxicity in brain organoids. The mechanism of action of these compounds involves interfering with late steps in the virus life cycle to inhibit the formation of new virus particles.

VIRUSES-BASEL (2021)

Article Clinical Neurology

The Spatial and Cell-Type Distribution of SARS-CoV-2 Receptor ACE2 in the Human and Mouse Brains

Rongrong Chen et al.

Summary: The distribution of ACE2 in human and mouse brains differs, which may play a crucial role in central nervous system symptoms in COVID-19 patients infected with SARS-CoV-2. Potential species differences should be taken into consideration when using mouse models to study the neurological effects of SARS-CoV-2 infection.

FRONTIERS IN NEUROLOGY (2021)

Article Clinical Neurology

Cognitive decline among individuals with history of mild symptomatic SARS-CoV-2 infection: A longitudinal prospective study nested to a population cohort

Oscar H. Del Brutto et al.

Summary: This study provides evidence of cognitive decline among individuals with mild symptomatic SARS-CoV-2 infection. The pathogenesis of this complication remains unknown. Seropositive individuals were found to have a higher risk of cognitive decline compared to seronegative individuals.

EUROPEAN JOURNAL OF NEUROLOGY (2021)

Review Genetics & Heredity

Regional specification and complementation with non-neuroectodermal cells in human brain organoids

Yoshiaki Tanaka et al.

Summary: The emergence of organoids and their application in biomedical research, particularly in the development of whole brain and specific brain region organoids, has been a fascinating theme. Advances in organoid technologies, including the incorporation of endothelial cells and microglia, have the potential to contribute significantly to the study of neuronal diseases.

JOURNAL OF MOLECULAR MEDICINE-JMM (2021)

Article Cell & Tissue Engineering

Revealing Tissue-Specific SARS-CoV-2 Infection and Host Responses using Human Stem Cell-Derived Lung and Cerebral Organoids

Shashi Kant Tiwari et al.

Summary: Researchers generated iPSC-derived lung and brain organoids, finding that lung organoids are highly permissive to SARS-CoV-2 infection, while brain organoids are less susceptible. These findings will aid in understanding the pathogenesis of COVID-19 and drug discovery.

STEM CELL REPORTS (2021)

Article Cell & Tissue Engineering

Neurotropic Effects of SARS-CoV-2 Modeled by the Human Brain Organoids

Anand Ramani et al.

Summary: SARS-CoV-2 targets human neurons and causes neurological symptoms, with human brain organoids playing a key role in research to enhance our understanding of this phenomenon.

STEM CELL REPORTS (2021)

Article Cell & Tissue Engineering

Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly

Veronica Krenn et al.

Summary: Viral infection in early pregnancy can lead to microcephaly, with distinct mechanisms observed in Zika virus and herpes simplex virus-induced brain organoid models. This study highlights the importance of organoid models in understanding virus-specific mechanisms and immune responses associated with virus-induced microcephaly.

CELL STEM CELL (2021)

Article Microbiology

Rottlerin inhibits La Crosse virus-induced encephalitis in mice and blocks release of replicating virus from the Golgi body in neurons

Durbadal Ojha et al.

Summary: Rottlerin has been identified as a potent inhibitor of LACV-induced neuronal cell death, with strong antiviral effects in multiple cell lines and even reducing viral replication. In mouse experiments, Rottlerin reduced disease development and replication of other pathogenic orthobunyaviruses, showing promise as a potential treatment for viral encephalitis.

NATURE MICROBIOLOGY (2021)

Review Microbiology

Methodologies for Generating Brain Organoids to Model Viral Pathogenesis in the CNS

Hannah K. Hopkins et al.

Summary: The human brain is a target for viruses, with neurological infections potentially leading to death or lifelong sequelae. Organoid models of the CNS can serve as platforms for viral pathogenesis research, reducing the need for animal experimentation.

PATHOGENS (2021)

Review Microbiology

Are the Organoid Models an Invaluable Contribution to ZIKA Virus Research?

Pasquale Marrazzo et al.

Summary: Studying Zika virus infection through organoids provides a valuable approach to understanding pathogenic mechanisms and developing strategies for prevention and treatment. Tissue-engineered models in a 3D perspective offer promising future biological systems to decipher pathogenic processes and evaluate preventive and therapeutic strategies against Zika virus.

PATHOGENS (2021)

Review Medicine, General & Internal

Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

Mohammed M. Almutairi et al.

Summary: COVID-19, caused by SARS-CoV-2, presents with various symptoms and can lead to pneumonia and respiratory failure. The cellular and molecular mechanisms of SARS-CoV-2-induced neuroinflammation are not yet fully understood, highlighting the need for further research in this area.

FRONTIERS IN MEDICINE (2021)

Review Virology

Review of studies of severe acute respiratory syndrome related coronavirus-2 pathogenesis in human organoid models

Ece Egilmezer et al.

Summary: The global pandemic of Covid-19 caused by SARS-CoV-2 has prompted urgent investigations into the pathogenesis of the disease and the development of therapeutic and vaccination strategies. Human organoid models provide a way to study the effects of SARS-CoV-2 on cellular infection and immune response, as well as potential antiviral treatments.

REVIEWS IN MEDICAL VIROLOGY (2021)

Article Cell & Tissue Engineering

SARS-CoV-2 targets glial cells in human cortical organoids

Courtney L. McMahon et al.

Summary: Researchers used human stem cell-derived brain organoids to study how SARS-CoV-2 infects brain tissue and found that glial cells and cells of the choroid plexus were preferentially targeted, while neurons were not infected. The expression of angiotensin-converting enzyme 2 was detected in infected cells, but viral replication and cell death did not occur, indicating that this model serves as a feasible platform to study the cellular effects of SARS-CoV-2 infection in brain tissue.

STEM CELL REPORTS (2021)

Article Public, Environmental & Occupational Health

La Crosse Virus Disease in the United States, 2003-2019

Grace M. Vahey et al.

Summary: La Crosse virus is a mosquito-transmitted virus that mainly affects children and causes encephalitis and meningitis. The virus is most commonly reported in the Great Lakes, mid-Atlantic, and southeastern regions of the United States. Surveillance data may underestimate the true incidence of LACV disease.

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE (2021)

Article Biochemistry & Molecular Biology

A human three-dimensional neural-perivascular 'assembloid' promotes astrocytic development and enables modeling of SARS-CoV-2 neuropathology

Lu Wang et al.

Summary: Research findings suggest that pericytes may serve as important portals for SARS-CoV-2 infection in the nervous system. Introducing pericyte-like cells (PLCs) into cortical organoids can provide an experimental model that supports virus entry and replication.

NATURE MEDICINE (2021)

Article Microbiology

Molecular Features of the Measles Virus Viral Fusion Complex That Favor Infection and Spread in the Brain

Cyrille Mathieu et al.

Summary: The study found that a single amino acid change in the fusion protein (F) of measles virus (MeV) can enhance the virus's ability to spread in the central nervous system, leading to serious complications. Furthermore, the research showed that virus spread in brain tissue can be blocked by an inhibitory peptide targeting the F protein.
Article Cell & Tissue Engineering

Developing human pluripotent stem cell-based cerebral organoids with a controllable microglia ratio for modeling brain development and pathology

Ranjie Xu et al.

Summary: By coculturing human pluripotent stem cell (hPSC)-derived microglia and primitive macrophage progenitors, a new brain region-specific organoid model containing microglia has been established. This model allows control of the number of human microglia, which exhibit phagocytic activity and synaptic pruning function. Additionally, human microglia in the organoids respond to Zika virus infection, providing a novel platform to study human microglial function in various neurological disorders.

STEM CELL REPORTS (2021)

Article Microbiology

Cerebral Organoids Derived from a Parkinson's Patient Exhibit Unique Pathogenesis from Chikungunya Virus Infection When Compared to a Non-Parkinson's Patient

Emily M. Schultz et al.

Summary: This study revealed that after Chikungunya virus infection, cerebral organoids from Parkinson's patients exhibited a different response compared to those from non-Parkinson's patients. Neurotransmission data showed dysregulation of IL-1, IL-10, and IL-6, potentially contributing to persistent depression in patients post-infection. Both types of organoids showed increased expression of CXCL10, which is linked to demyelination.

PATHOGENS (2021)

Article Parasitology

Arbovirus, herpesvirus, and enterovirus associated with neurological syndromes in adult patients of a university hospital, 2017-2018

Lucas Lopes Leon et al.

Summary: Viral genomes were detected in 35.2% of cerebrospinal fluid samples from patients with suspected nervous system infections, emphasizing the high prevalence of viruses in the nervous system and the importance of nucleic acid amplification tests for detecting viral agents in CSF samples.

REVISTA DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL (2021)

Article Infectious Diseases

Encephalitis in Thailand: A Neglected Disease Increasingly Caused by Enterovirus

Pasin Hemachudha et al.

Summary: The Thai Red Cross, in collaboration with the Ministry of Public Health, conducted encephalitis surveillance and found that enteroviruses have become a major cause of viral encephalitis. The shift in viral neurotropism pattern leading to this change was unexpected.

TROPICAL MEDICINE AND INFECTIOUS DISEASE (2021)

Review Cell Biology

Toward three-dimensional in vitro models to study neurovascular unit functions in health and disease

Tara M. Caffrey et al.

Summary: The brain's high metabolic demands require an efficient vascular system to supply nutrients and oxygen, which is regulated by the neurovascular unit composed of neurons, glial and vascular cells. Changes in neurovascular unit functions in neurodegenerative diseases can impair neurovascular coupling, blood-brain barrier permeability, cerebral blood flow, and waste clearance. Advanced physiologically-relevant human models of the neurovascular unit are being developed using stem-cell derived organoids and vascularized organoids to better understand disease processes and potential therapeutic strategies. Continued innovation in engineering and design is necessary to create more complex models for studying neurovascular unit functionality.

NEURAL REGENERATION RESEARCH (2021)

Review Immunology

Human stem cell models to study host-virus interactions in the central nervous system

Oliver Harschnitz et al.

Summary: The review explains the use of human pluripotent stem cell technology in studying antiviral immunity in the central nervous system. This technology offers a unique opportunity for researching new therapies and mechanisms of CNS viral infections, including those associated with SARS-CoV-2. The advancements in this technology allow for studying host-virus interactions and complex disease mechanisms in disease-relevant cells of the human CNS.

NATURE REVIEWS IMMUNOLOGY (2021)

Letter Cell Biology

SARS-CoV-2 infects human neural progenitor cells and brain organoids

Bao-Zhong Zhang et al.

CELL RESEARCH (2020)

Article Virology

Patterns of Herpes Simplex Virus 1 Infection in Neural Progenitor Cells

Wenxiao Zheng et al.

JOURNAL OF VIROLOGY (2020)

Article Biochemistry & Molecular Biology

SARS-CoV-2 targets neurons of 3D human brain organoids

Anand Ramani et al.

EMBO JOURNAL (2020)

Article Infectious Diseases

Role of microglia in the dissemination of Zika virus from mother to fetal brain

Pei Xu et al.

PLOS NEGLECTED TROPICAL DISEASES (2020)

Article Medicine, Research & Experimental

Cerebral Organoids: A Human Model for AAV Capsid Selection and Therapeutic Transgene Efficacy in the Brain

Josse A. Depla et al.

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT (2020)

Editorial Material Virology

A Perspective on Organoids for Virology Research

Adithya Sridhar et al.

VIRUSES-BASEL (2020)

Article Multidisciplinary Sciences

Multiscale 3D phenotyping of human cerebral organoids

Alexandre Albanese et al.

SCIENTIFIC REPORTS (2020)

Article Immunology

Betulinic Acid Exerts Cytoprotective Activity on Zika Virus-Infected Neural Progenitor Cells

Bruno R. R. Cavalcante et al.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2020)

Article Medicine, Research & Experimental

Infectability of Human BrainSphere Neurons Suggests Neurotropism of SARS-CoV-2

C. Korin Bullen et al.

ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION (2020)

Article Biochemistry & Molecular Biology

Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution

Alex A. Pollen et al.

Article Microbiology

Determinants of Zika virus host tropism uncovered by deep mutational scanning

Yin Xiang Setoh et al.

NATURE MICROBIOLOGY (2019)

Article Biochemistry & Molecular Biology

Protection of ZIKV infection-induced neuropathy by abrogation of acute antiviral response in human neural progenitors

Ling Liu et al.

CELL DEATH AND DIFFERENTIATION (2019)

Review Developmental Biology

Brain organoids: advances, applications and challenges

Xuyu Qian et al.

DEVELOPMENT (2019)

Review Biochemistry & Molecular Biology

New Insights into Measles Virus Brain Infections

Shumpei Watanabe et al.

TRENDS IN MICROBIOLOGY (2019)

Review Immunology

The role of microglia in viral encephalitis: a review

Zhuangzhuang Chen et al.

JOURNAL OF NEUROINFLAMMATION (2019)

Article Virology

Human Cytomegalovirus Compromises Development of Cerebral Organoids

Rebecca M. Brown et al.

JOURNAL OF VIROLOGY (2019)

Article Biotechnology & Applied Microbiology

Virus stamping for targeted single-cell infection in vitro and in vivo

Rajib Schubert et al.

NATURE BIOTECHNOLOGY (2018)

Article Neurosciences

Six-month cultured cerebral organoids from human ES cells contain matured neural cells

Takeshi K. Matsui et al.

NEUROSCIENCE LETTERS (2018)

Review Obstetrics & Gynecology

Neonatal herpes simplex virus infections

Swetha G. Pinninti et al.

SEMINARS IN PERINATOLOGY (2018)

Article Engineering, Biomedical

Effects of 3D culturing conditions on the transcriptomic profile of stem-cell-derived neurons

Halil Tekin et al.

NATURE BIOMEDICAL ENGINEERING (2018)

Article Clinical Neurology

Viral Encephalitis

Arun Venkatesan et al.

NEUROLOGIC CLINICS (2018)

Article Multidisciplinary Sciences

Microglia innately develop within cerebral organoids

Paul R. Ormel et al.

NATURE COMMUNICATIONS (2018)

Article Microbiology

Microglia Increase Inflammatory Responses in iPSC-Derived Human BrainSpheres

Celina Monteiro Abreu et al.

FRONTIERS IN MICROBIOLOGY (2018)

Letter Immunology

Symptomatic Dengue during Pregnancy and Congenital Neurologic Malformations

Enny S. Paixao et al.

EMERGING INFECTIOUS DISEASES (2018)

Review Multidisciplinary Sciences

The rise of three-dimensional human brain cultures

Sergiu P. Pasca

NATURE (2018)

Letter Radiology, Nuclear Medicine & Medical Imaging

Neuroimaging findings of Zika virus infection

Viroj Wiwanitkit

JAPANESE JOURNAL OF RADIOLOGY (2017)

Letter Radiology, Nuclear Medicine & Medical Imaging

Neuroimaging findings of Zika virus infection

Viroj Wiwanitkit

JAPANESE JOURNAL OF RADIOLOGY (2017)

Review Neurosciences

The use of brain organoids to investigate neural development and disease

Elizabeth Di Lullo et al.

NATURE REVIEWS NEUROSCIENCE (2017)

Review Neurosciences

Viral vectors for therapy of neurologic diseases

Sourav R. Choudhury et al.

NEUROPHARMACOLOGY (2017)

Review Immunology

Neurological Manifestations of Dengue Infection

Guo-Hong Li et al.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2017)

Article Multidisciplinary Sciences

Modelling Zika Virus Infection of the Developing Human Brain In Vitro Using Stem Cell Derived Cerebral Organoids

Max R. Salick et al.

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS (2017)

Article Multidisciplinary Sciences

The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

Carolina Q. Sacramento et al.

SCIENTIFIC REPORTS (2017)

Article Cell & Tissue Engineering

Induction of Expansion and Folding in Human Cerebral Organoids

Yun Li et al.

CELL STEM CELL (2017)

Article Biochemistry & Molecular Biology

Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure

Xuyu Qian et al.

Article Cell & Tissue Engineering

Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice

Cui Li et al.

CELL STEM CELL (2016)

Review Virology

Zika Virus-Induced Microcephaly and Its Possible Molecular Mechanism

Md Imam Faizan et al.

INTERVIROLOGY (2016)

Article Multidisciplinary Sciences

The Brazilian Zika virus strain causes birth defects in experimental models

Fernanda R. Cugola et al.

NATURE (2016)

Article Multidisciplinary Sciences

A complement-microglial axis drives synapse loss during virus-induced memory impairment

Michael J. Vasek et al.

NATURE (2016)

Article Medicine, General & Internal

Zika Virus Associated with Microcephaly

Jernej Mlakar et al.

NEW ENGLAND JOURNAL OF MEDICINE (2016)

Article Multidisciplinary Sciences

Zika virus impairs growth in human neurospheres and brain organoids

Patricia P. Garcez et al.

SCIENCE (2016)

Article Biochemical Research Methods

Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture

Anca M. Pasca et al.

NATURE METHODS (2015)

Article Virology

Viral diseases of the central nervous system

Phillip A. Swanson et al.

CURRENT OPINION IN VIROLOGY (2015)

Article Immunology

Congenital Cytomegalovirus Infection: Clinical Outcome

Suresh B. Boppana et al.

CLINICAL INFECTIOUS DISEASES (2013)

Article Multidisciplinary Sciences

Cerebral organoids model human brain development and microcephaly

Madeline A. Lancaster et al.

NATURE (2013)

Review Physiology

Physiology of Microglia

Helmut Kettenmann et al.

PHYSIOLOGICAL REVIEWS (2011)