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  1. Article ; Online: Modeling Multi-organ Infection by SARS-CoV-2 Using Stem Cell Technology.

    Simoneau, Camille R / Ott, Melanie

    Cell stem cell

    2020  Volume 27, Issue 6, Page(s) 859–868

    Abstract: SARS-CoV-2, the virus causing the current COVID-19 pandemic, primarily targets the airway epithelium and in lungs can lead to acute respiratory distress syndrome. Clinical studies in recent months have revealed that COVID-19 is a multi-organ disease ... ...

    Abstract SARS-CoV-2, the virus causing the current COVID-19 pandemic, primarily targets the airway epithelium and in lungs can lead to acute respiratory distress syndrome. Clinical studies in recent months have revealed that COVID-19 is a multi-organ disease causing characteristic complications. Stem cell models of various organ systems-most prominently, lung, gut, heart, and brain-are at the forefront of studies aimed at understanding the role of direct infection in COVID-19 multi-organ dysfunction.
    MeSH term(s) COVID-19/complications ; COVID-19/physiopathology ; Humans ; Models, Biological ; Stem Cells
    Language English
    Publishing date 2020-12-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2020.11.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6589: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 75: Show issues

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  2. Article ; Online: Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system.

    Natarajan, Vaishaali / Simoneau, Camille R / Erickson, Ann L / Meyers, Nathan L / Baron, Jody L / Cooper, Stewart / McDevitt, Todd C / Ott, Melanie

    Open biology

    2022  Volume 12, Issue 3, Page(s) 210320

    Abstract: Hepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV ... ...

    Abstract Hepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV since
    MeSH term(s) CD8-Positive T-Lymphocytes/immunology ; Coculture Techniques ; Hepacivirus ; Hepatitis C/immunology ; Humans ; Microfluidics ; Organoids ; Viral Nonstructural Proteins/immunology
    Chemical Substances Viral Nonstructural Proteins
    Language English
    Publishing date 2022-03-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2630944-0
    ISSN 2046-2441 ; 2046-2441
    ISSN (online) 2046-2441
    ISSN 2046-2441
    DOI 10.1098/rsob.210320
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Nuclear accumulation of host transcripts during Zika Virus Infection.

    Leon, Kristoffer E / Khalid, Mir M / Flynn, Ryan A / Fontaine, Krystal A / Nguyen, Thong T / Kumar, G Renuka / Simoneau, Camille R / Tomar, Sakshi / Jimenez-Morales, David / Dunlap, Mariah / Kaye, Julia / Shah, Priya S / Finkbeiner, Steven / Krogan, Nevan J / Bertozzi, Carolyn / Carette, Jan E / Ott, Melanie

    PLoS pathogens

    2023  Volume 19, Issue 1, Page(s) e1011070

    Abstract: Zika virus (ZIKV) infects fetal neural progenitor cells (NPCs) causing severe neurodevelopmental disorders in utero. Multiple pathways involved in normal brain development are dysfunctional in infected NPCs but how ZIKV centrally reprograms these ... ...

    Abstract Zika virus (ZIKV) infects fetal neural progenitor cells (NPCs) causing severe neurodevelopmental disorders in utero. Multiple pathways involved in normal brain development are dysfunctional in infected NPCs but how ZIKV centrally reprograms these pathways remains unknown. Here we show that ZIKV infection disrupts subcellular partitioning of host transcripts critical for neurodevelopment in NPCs and functionally link this process to the up-frameshift protein 1 (UPF1). UPF1 is an RNA-binding protein known to regulate decay of cellular and viral RNAs and is less expressed in ZIKV-infected cells. Using infrared crosslinking immunoprecipitation and RNA sequencing (irCLIP-Seq), we show that a subset of mRNAs loses UPF1 binding in ZIKV-infected NPCs, consistent with UPF1's diminished expression. UPF1 target transcripts, however, are not altered in abundance but in subcellular localization, with mRNAs accumulating in the nucleus of infected or UPF1 knockdown cells. This leads to diminished protein expression of FREM2, a protein required for maintenance of NPC identity. Our results newly link UPF1 to the regulation of mRNA transport in NPCs, a process perturbed during ZIKV infection.
    MeSH term(s) Humans ; Brain/metabolism ; Brain/virology ; Neural Stem Cells/virology ; RNA Helicases/genetics ; RNA Helicases/metabolism ; Trans-Activators/metabolism ; Virus Replication ; Zika Virus/physiology ; Zika Virus Infection/genetics
    Chemical Substances RNA Helicases (EC 3.6.4.13) ; Trans-Activators ; UPF1 protein, human (EC 3.6.4.13)
    Language English
    Publishing date 2023-01-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011070
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Hepatitis C virus infects and perturbs liver stem cells.

    Meyers, Nathan L / Ashuach, Tal / Lyons, Danielle E / Khalid, Mir M / Simoneau, Camille R / Erickson, Ann L / Bouhaddou, Mehdi / Nguyen, Thong T / Kumar, G Renuka / Taha, Taha Y / Natarajan, Vaishaali / Baron, Jody L / Neff, Norma / Zanini, Fabio / Mahmoudi, Tokameh / Quake, Stephen R / Krogan, Nevan J / Cooper, Stewart / McDevitt, Todd C /
    Yosef, Nir / Ott, Melanie

    mBio

    2023  , Page(s) e0131823

    Abstract: Hepatitis C virus (HCV) is the leading cause of death from liver disease. How HCV infection causes lasting liver damage and increases cancer risk remains unclear. Here, we identify bipotent liver stem cells as novel targets for HCV infection, and their ... ...

    Abstract Hepatitis C virus (HCV) is the leading cause of death from liver disease. How HCV infection causes lasting liver damage and increases cancer risk remains unclear. Here, we identify bipotent liver stem cells as novel targets for HCV infection, and their erroneous differentiation as the potential cause of impaired liver regeneration and cancer development. We show 3D organoids generated from liver stem cells from actively HCV-infected individuals carry replicating virus and maintain low-grade infection over months. Organoids can be infected with a primary HCV isolate. Virus-inclusive single-cell RNA sequencing uncovered transcriptional reprogramming in HCV
    Language English
    Publishing date 2023-11-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.01318-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Immediate myeloid depot for SARS-CoV-2 in the human lung.

    Magnen, Mélia / You, Ran / Rao, Arjun A / Davis, Ryan T / Rodriguez, Lauren / Simoneau, Camille R / Hysenaj, Lisiena / Hu, Kenneth H / Love, Christina / Woodruff, Prescott G / Erle, David J / Hendrickson, Carolyn M / Calfee, Carolyn S / Matthay, Michael A / Roose, Jeroen P / Sil, Anita / Ott, Melanie / Langelier, Charles R / Krummel, Matthew F /
    Looney, Mark R

    Research square

    2022  

    Abstract: In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ... ...

    Abstract In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic
    Language English
    Publishing date 2022-05-17
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-1639631/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Functional genomic screens identify human host factors for SARS-CoV-2 and common cold coronaviruses.

    Wang, Ruofan / Simoneau, Camille R / Kulsuptrakul, Jessie / Bouhaddou, Mehdi / Travisano, Katherine / Hayashi, Jennifer M / Carlson-Stevermer, Jared / Oki, Jennifer / Holden, Kevin / Krogan, Nevan J / Ott, Melanie / Puschnik, Andreas S

    bioRxiv : the preprint server for biology

    2020  

    Abstract: ... ...

    Abstract The
    Keywords covid19
    Language English
    Publishing date 2020-09-24
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2020.09.24.312298
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system

    Vaishaali Natarajan / Camille R. Simoneau / Ann L. Erickson / Nathan L. Meyers / Jody L. Baron / Stewart Cooper / Todd C. McDevitt / Melanie Ott

    Open Biology, Vol 12, Iss

    2022  Volume 3

    Abstract: Hepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV since in vivo ... ...

    Abstract Hepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV since in vivo animal models are limited and in vitro cancer cell models often show dysregulated immune and proliferative responses. Here, we developed a CD8+ T cell and adult stem cell liver organoid system using a microfluidic chip to coculture 3D human liver organoids embedded in extracellular matrix with HLA-matched primary human T cells in suspension. We then employed automated phase contrast and immunofluorescence imaging to monitor T cell invasion and morphological changes in the liver organoids. This microfluidic coculture system supports targeted killing of liver organoids when pulsed with a peptide specific for HCV non-structural protein 3 (NS3) (KLVALGINAV) in the presence of patient-derived CD8+ T cells specific for KLVALGINAV. This demonstrates the novel potential of the coculture system to molecularly study adaptive immune responses to HCV in an in vitro setting using primary human cells.
    Keywords hepatitis C ; liver organoid ; CD8+ T cells ; microfluidics ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher The Royal Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Nuclear accumulation of host transcripts during Zika Virus Infection.

    Kristoffer E Leon / Mir M Khalid / Ryan A Flynn / Krystal A Fontaine / Thong T Nguyen / G Renuka Kumar / Camille R Simoneau / Sakshi Tomar / David Jimenez-Morales / Mariah Dunlap / Julia Kaye / Priya S Shah / Steven Finkbeiner / Nevan J Krogan / Carolyn Bertozzi / Jan E Carette / Melanie Ott

    PLoS Pathogens, Vol 19, Iss 1, p e

    2023  Volume 1011070

    Abstract: Zika virus (ZIKV) infects fetal neural progenitor cells (NPCs) causing severe neurodevelopmental disorders in utero. Multiple pathways involved in normal brain development are dysfunctional in infected NPCs but how ZIKV centrally reprograms these ... ...

    Abstract Zika virus (ZIKV) infects fetal neural progenitor cells (NPCs) causing severe neurodevelopmental disorders in utero. Multiple pathways involved in normal brain development are dysfunctional in infected NPCs but how ZIKV centrally reprograms these pathways remains unknown. Here we show that ZIKV infection disrupts subcellular partitioning of host transcripts critical for neurodevelopment in NPCs and functionally link this process to the up-frameshift protein 1 (UPF1). UPF1 is an RNA-binding protein known to regulate decay of cellular and viral RNAs and is less expressed in ZIKV-infected cells. Using infrared crosslinking immunoprecipitation and RNA sequencing (irCLIP-Seq), we show that a subset of mRNAs loses UPF1 binding in ZIKV-infected NPCs, consistent with UPF1's diminished expression. UPF1 target transcripts, however, are not altered in abundance but in subcellular localization, with mRNAs accumulating in the nucleus of infected or UPF1 knockdown cells. This leads to diminished protein expression of FREM2, a protein required for maintenance of NPC identity. Our results newly link UPF1 to the regulation of mRNA transport in NPCs, a process perturbed during ZIKV infection.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Immediate myeloid depot for SARS-CoV-2 in the human lung.

    Magnen, Mélia / You, Ran / Rao, Arjun A / Davis, Ryan T / Rodriguez, Lauren / Simoneau, Camille R / Hysenaj, Lisiena / Hu, Kenneth H / Love, Christina / Woodruff, Prescott G / Erle, David J / Hendrickson, Carolyn M / Calfee, Carolyn S / Matthay, Michael A / Roose, Jeroen P / Sil, Anita / Ott, Melanie / Langelier, Charles R / Krummel, Matthew F /
    Looney, Mark R

    bioRxiv : the preprint server for biology

    2022  

    Abstract: In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, considerable focus has been placed on a model of viral entry into host epithelial populations, with a separate focus upon the responding immune system dysfunction that ... ...

    Abstract In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, considerable focus has been placed on a model of viral entry into host epithelial populations, with a separate focus upon the responding immune system dysfunction that exacerbates or causes disease. We developed a precision-cut lung slice model to investigate very early host-viral pathogenesis and found that SARS-CoV-2 had a rapid and specific tropism for myeloid populations in the human lung. Infection of alveolar macrophages was partially dependent upon their expression of ACE2, and the infections were productive for amplifying virus, both findings which were in contrast with their neutralization of another pandemic virus, Influenza A virus (IAV). Compared to IAV, SARS-CoV-2 was extremely poor at inducing interferon-stimulated genes in infected myeloid cells, providing a window of opportunity for modest titers to amplify within these cells. Endotracheal aspirate samples from humans with the acute respiratory distress syndrome (ARDS) from COVID-19 confirmed the lung slice findings, revealing a persistent myeloid depot. In the early phase of SARS-CoV-2 infection, myeloid cells may provide a safe harbor for the virus with minimal immune stimulatory cues being generated, resulting in effective viral colonization and quenching of the immune system.
    Language English
    Publishing date 2022-05-11
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.04.28.489942
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes.

    Andrews, Madeline G / Mukhtar, Tanzila / Eze, Ugomma C / Simoneau, Camille R / Perez, Yonatan / Mostajo-Radji, Mohammed A / Wang, Shaohui / Velmeshev, Dmitry / Salma, Jahan / Kumar, G Renuka / Pollen, Alex A / Crouch, Elizabeth E / Ott, Melanie / Kriegstein, Arnold R

    bioRxiv : the preprint server for biology

    2021  

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. It proves fatal for one percent of those ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. It proves fatal for one percent of those infected. Neurological symptoms, which range in severity, accompany a significant proportion of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized primary human cortical tissue and stem cell-derived cortical organoids. We find significant and predominant infection in cortical astrocytes in both primary and organoid cultures, with minimal infection of other cortical populations. Infected astrocytes had a corresponding increase in reactivity characteristics, growth factor signaling, and cellular stress. Although human cortical cells, including astrocytes, have minimal ACE2 expression, we find high levels of alternative coronavirus receptors in infected astrocytes, including DPP4 and CD147. Inhibition of DPP4 reduced infection and decreased expression of the cell stress marker, ARCN1. We find tropism of SARS-CoV-2 for human astrocytes mediated by DPP4, resulting in reactive gliosis-type injury.
    Language English
    Publishing date 2021-01-18
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.01.17.427024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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