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  1. AU="Mirko Cortese"
  2. AU="Klein, Steffen"
  3. AU="Koike, Toru"
  4. AU="Hung, Chung-Yu"
  5. AU="Muendlein, Hayley I"
  6. AU="Papavramidis, Theodosios"

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  1. Artikel ; Online: Exploiting a chink in the armor

    Mirko Cortese / Christopher J. Neufeldt

    Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-

    engineering broadly neutralizing monoclonal antibodies for SARS-like viruses

    2021  Band 2

    Schlagwörter Medicine ; R ; Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2021-06-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Replication-Independent Generation and Morphological Analysis of Flavivirus Replication Organelles

    Sarah Goellner / Berati Cerikan / Mirko Cortese / Christopher J. Neufeldt / Uta Haselmann / Ralf Bartenschlager

    STAR Protocols, Vol 1, Iss 3, Pp 100173- (2020)

    2020  

    Abstract: Summary: Positive-strand RNA viruses replicate in distinct membranous structures called replication organelles (ROs). Mechanistic studies of RO formation have been difficult because perturbations affecting viral replication have an impact on viral ... ...

    Abstract Summary: Positive-strand RNA viruses replicate in distinct membranous structures called replication organelles (ROs). Mechanistic studies of RO formation have been difficult because perturbations affecting viral replication have an impact on viral protein amounts, thus affecting RO biogenesis. Here, we present a detailed guide on how to use a replication-independent expression system, designated pIRO (plasmid-induced replication organelle formation), inducing bona fide flavivirus ROs in transfected cells. This will be useful for mechanistic studies of viral and cellular factors driving flavivirus RO biogenesis.For complete details on the use and execution of this protocol, please refer to Cerikan et al. (2020).
    Schlagwörter Cell Biology ; Microscopy ; Molecular Biology ; Science (General) ; Q1-390
    Sprache Englisch
    Erscheinungsdatum 2020-12-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: A protocol for full-rotation soft X-ray tomography of single cells

    Jian-Hua Chen / Bieke Vanslembrouck / Valentina Loconte / Axel Ekman / Mirko Cortese / Ralf Bartenschlager / Gerry McDermott / Carolyn A. Larabell / Mark A. Le Gros / Venera Weinhardt

    STAR Protocols, Vol 3, Iss 1, Pp 101176- (2022)

    2022  

    Abstract: Summary: The protocol describes step-by-step sample preparation, data acquisition, and segmentation of cellular organelles with soft X-ray tomography. It is designed for microscopes built to perform full-rotation data acquisition on specimens in ... ...

    Abstract Summary: The protocol describes step-by-step sample preparation, data acquisition, and segmentation of cellular organelles with soft X-ray tomography. It is designed for microscopes built to perform full-rotation data acquisition on specimens in cylindrical sample holders, such as the XM-2 microscope at the Advanced Light Source, LBNL; however, it might be generalized for similar sample holder designs for both synchrotron and table-top microscopes.For complete details on the use and execution of this profile, please refer to Loconte et al. (2021).
    Schlagwörter Cell Biology ; Single Cell ; Microscopy ; Science (General) ; Q1-390
    Sprache Englisch
    Erscheinungsdatum 2022-03-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: A novel interaction between dengue virus nonstructural protein 1 and the NS4A-2K-4B precursor is required for viral RNA replication but not for formation of the membranous replication organelle.

    Anna Płaszczyca / Pietro Scaturro / Christopher John Neufeldt / Mirko Cortese / Berati Cerikan / Salvatore Ferla / Andrea Brancale / Andreas Pichlmair / Ralf Bartenschlager

    PLoS Pathogens, Vol 15, Iss 5, p e

    2019  Band 1007736

    Abstract: Dengue virus (DENV) has emerged as major human pathogen. Despite the serious socio-economic impact of DENV-associated diseases, antiviral therapy is missing. DENV replicates in the cytoplasm of infected cells and induces a membranous replication ... ...

    Abstract Dengue virus (DENV) has emerged as major human pathogen. Despite the serious socio-economic impact of DENV-associated diseases, antiviral therapy is missing. DENV replicates in the cytoplasm of infected cells and induces a membranous replication organelle, formed by invaginations of the endoplasmic reticulum membrane and designated vesicle packets (VPs). Nonstructural protein 1 (NS1) of DENV is a multifunctional protein. It is secreted from cells to counteract antiviral immune responses, but also critically contributes to the severe clinical manifestations of dengue. In addition, NS1 is indispensable for viral RNA replication, but the underlying molecular mechanism remains elusive. In this study, we employed a combination of genetic, biochemical and imaging approaches to dissect the determinants in NS1 contributing to its various functions in the viral replication cycle. Several important observations were made. First, we identified a cluster of amino acid residues in the exposed region of the β-ladder domain of NS1 that are essential for NS1 secretion. Second, we revealed a novel interaction of NS1 with the NS4A-2K-4B cleavage intermediate, but not with mature NS4A or NS4B. This interaction is required for RNA replication, with two residues within the connector region of the NS1 "Wing" domain being crucial for binding of the NS4A-2K-4B precursor. By using a polyprotein expression system allowing the formation of VPs in the absence of viral RNA replication, we show that the NS1 -NS4A-2K-4B interaction is not required for VP formation, arguing that the association between these two proteins plays a more direct role in the RNA amplification process. Third, through analysis of polyproteins containing deletions in NS1, and employing a trans-complementation assay, we show that both cis and trans acting elements within NS1 contribute to VP formation, with the capability of NS1 mutants to form VPs correlating with their capability to support RNA replication. In conclusion, these results reveal a direct role of NS1 in ...
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2019-05-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography

    Steffen Klein / Mirko Cortese / Sophie L. Winter / Moritz Wachsmuth-Melm / Christopher J. Neufeldt / Berati Cerikan / Megan L. Stanifer / Steeve Boulant / Ralf Bartenschlager / Petr Chlanda

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Band 10

    Abstract: Here the authors visualize SARS-CoV-2 infected cells by in situ cryo-electron tomography, delineating the structural organization and conformational changes that occur during virus replication and budding; and provide insight into vRNP architecture and ... ...

    Abstract Here the authors visualize SARS-CoV-2 infected cells by in situ cryo-electron tomography, delineating the structural organization and conformational changes that occur during virus replication and budding; and provide insight into vRNP architecture and RNA networks in double membrane vesicles.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2020-11-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB

    Christopher J. Neufeldt / Berati Cerikan / Mirko Cortese / Jamie Frankish / Ji-Young Lee / Agnieszka Plociennikowska / Florian Heigwer / Vibhu Prasad / Sebastian Joecks / Sandy S. Burkart / David Y. Zander / Baskaran Subramanian / Rayomand Gimi / Seetharamaiyer Padmanabhan / Radhakrishnan Iyer / Mathieu Gendarme / Bachir El Debs / Niels Halama / Uta Merle /
    Michael Boutros / Marco Binder / Ralf Bartenschlager

    Communications Biology, Vol 5, Iss 1, Pp 1-

    2022  Band 15

    Abstract: Neufeldt et al. evaluate transcriptional and cytokine secretion profiles of cells and patient sera following SARS-CoV-2 infection and detect distinct upregulation of inflammatory cytokines. They also demonstrate that this upregulation is mediated by cGAS- ...

    Abstract Neufeldt et al. evaluate transcriptional and cytokine secretion profiles of cells and patient sera following SARS-CoV-2 infection and detect distinct upregulation of inflammatory cytokines. They also demonstrate that this upregulation is mediated by cGAS-STING and NF-κB signalling, which could provide a potential avenue for the development of future therapies against SARS-CoV-2.
    Schlagwörter Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2022-01-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Dengue Virus Non-structural Protein 1 Modulates Infectious Particle Production via Interaction with the Structural Proteins.

    Pietro Scaturro / Mirko Cortese / Laurent Chatel-Chaix / Wolfgang Fischl / Ralf Bartenschlager

    PLoS Pathogens, Vol 11, Iss 11, p e

    2015  Band 1005277

    Abstract: Non-structural protein 1 (NS1) is one of the most enigmatic proteins of the Dengue virus (DENV), playing distinct functions in immune evasion, pathogenesis and viral replication. The recently reported crystal structure of DENV NS1 revealed its peculiar ... ...

    Abstract Non-structural protein 1 (NS1) is one of the most enigmatic proteins of the Dengue virus (DENV), playing distinct functions in immune evasion, pathogenesis and viral replication. The recently reported crystal structure of DENV NS1 revealed its peculiar three-dimensional fold; however, detailed information on NS1 function at different steps of the viral replication cycle is still missing. By using the recently reported crystal structure, as well as amino acid sequence conservation, as a guide for a comprehensive site-directed mutagenesis study, we discovered that in addition to being essential for RNA replication, DENV NS1 is also critically required for the production of infectious virus particles. Taking advantage of a trans-complementation approach based on fully functional epitope-tagged NS1 variants, we identified previously unreported interactions between NS1 and the structural proteins Envelope (E) and precursor Membrane (prM). Interestingly, coimmunoprecipitation revealed an additional association with capsid, arguing that NS1 interacts via the structural glycoproteins with DENV particles. Results obtained with mutations residing either in the NS1 Wing domain or in the β-ladder domain suggest that NS1 might have two distinct functions in the assembly of DENV particles. By using a trans-complementation approach with a C-terminally KDEL-tagged ER-resident NS1, we demonstrate that the secretion of NS1 is dispensable for both RNA replication and infectious particle production. In conclusion, our results provide an extensive genetic map of NS1 determinants essential for viral RNA replication and identify a novel role of NS1 in virion production that is mediated via interaction with the structural proteins. These studies extend the list of NS1 functions and argue for a central role in coordinating replication and assembly/release of infectious DENV particles.
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2015-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Reciprocal Effects of Fibroblast Growth Factor Receptor Signaling on Dengue Virus Replication and Virion Production

    Mirko Cortese / Anil Kumar / Petr Matula / Lars Kaderali / Pietro Scaturro / Holger Erfle / Eliana Gisela Acosta / Sandra Buehler / Alessia Ruggieri / Laurent Chatel-Chaix / Karl Rohr / Ralf Bartenschlager

    Cell Reports, Vol 27, Iss 9, Pp 2579-2592.e

    2019  Band 6

    Abstract: Summary: Dengue virus (DENV) is a human arboviral pathogen accounting for 390 million infections every year. The available vaccine has limited efficacy, and DENV-specific drugs have not been generated. To better understand DENV-host cell interaction, we ... ...

    Abstract Summary: Dengue virus (DENV) is a human arboviral pathogen accounting for 390 million infections every year. The available vaccine has limited efficacy, and DENV-specific drugs have not been generated. To better understand DENV-host cell interaction, we employed RNA interference-based screening of the human kinome and identified fibroblast growth factor receptor 4 (FGFR4) to control the DENV replication cycle. Pharmacological inhibition of FGFR exerts a reciprocal effect by reducing DENV RNA replication and promoting the production of infectious virus particles. Addressing the latter effect, we found that the FGFR signaling pathway modulates intracellular distribution of DENV particles in a PI3K-dependent manner. Upon FGFR inhibition, virions accumulate in the trans-Golgi network compartment, where they undergo enhanced maturation cleavage of the envelope protein precursor membrane (prM), rendering virus particles more infectious. This study reveals an unexpected reciprocal role of a cellular receptor tyrosine kinase regulating DENV RNA replication and the production of infectious virions. : Cortese et al. conduct a human kinome RNAi-based screen and identify fibroblast growth factor receptor 4 (FGFR4) as a kinase that has a reciprocal effect on the DENV life cycle. Inhibition of the FGFR pathway reduces RNA replication while increasing production of infectious virus particles through enhanced proteolytic cleavage of prM. Keywords: RNAi-based screen, human kinome, DENV, flaviviruses, restriction factors, dependency factors, FGFR-4, host-pathogen interactions, furin, proteolytic cleavage
    Schlagwörter Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2019-05-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: Recombinant human cytomegalovirus (HCMV) RL13 binds human immunoglobulin G Fc.

    Mirko Cortese / Stefano Calò / Romina D'Aurizio / Anders Lilja / Nicola Pacchiani / Marcello Merola

    PLoS ONE, Vol 7, Iss 11, p e

    2012  Band 50166

    Abstract: The human cytomegalovirus (HCMV) protein RL13 has recently been described to be present in all primary isolates but rapidly mutated in culture adapted viruses. Although these data suggest a crucial role for this gene product in HCMV primary infection, no ...

    Abstract The human cytomegalovirus (HCMV) protein RL13 has recently been described to be present in all primary isolates but rapidly mutated in culture adapted viruses. Although these data suggest a crucial role for this gene product in HCMV primary infection, no function has so far been assigned to this protein. Working with RL13 expressed in isolation in transfected human epithelial cells, we demonstrated that recombinant RL13 from the clinical HCMV isolates TR and Merlin have selective human immunoglobulin (Ig)-binding properties towards IgG1 and IgG2 subtypes. An additional Fc binding protein, RL12, was also identified as an IgG1 and IgG2 binding protein but not further characterized. The glycoprotein RL13 trafficked to the plasma membrane where it bound and internalized exogenous IgG or its constant fragment (Fcγ). Analysis of RL13 ectodomain mutants suggested that the RL13 Ig-like domain is responsible for the Fc binding activity. Ligand-dependent internalization relied on a YxxL endocytic motif located in the C-terminal tail of RL13. Additionally, we showed that the tyrosine residue could be replaced by phenylalanine but not by alanine, indicating that the internalization signal was independent from phosphorylation events. In sum, RL13 binds human IgG and may contribute to HCMV immune evasion in the infected host, but this function does not readily explain the instability of the RL13 gene during viral propagation in cultured cells.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment

    Ji-Young Lee / Mirko Cortese / Uta Haselmann / Keisuke Tabata / Inés Romero-Brey / Charlotta Funaya / Nicole L. Schieber / Yu Qiang / Marie Bartenschlager / Stephanie Kallis / Christian Ritter / Karl Rohr / Yannick Schwab / Alessia Ruggieri / Ralf Bartenschlager

    Cell Reports, Vol 27, Iss 12, Pp 3602-3617.e

    2019  Band 5

    Abstract: Summary: The hepatitis C virus (HCV) is a major cause of chronic liver disease, affecting around 71 million people worldwide. Viral RNA replication occurs in a membranous compartment composed of double-membrane vesicles (DMVs), whereas virus particles ... ...

    Abstract Summary: The hepatitis C virus (HCV) is a major cause of chronic liver disease, affecting around 71 million people worldwide. Viral RNA replication occurs in a membranous compartment composed of double-membrane vesicles (DMVs), whereas virus particles are thought to form by budding into the endoplasmic reticulum (ER). It is unknown how these steps are orchestrated in space and time. Here, we established an imaging system to visualize HCV structural and replicase proteins in live cells and with high resolution. We determined the conditions for the recruitment of viral proteins to putative assembly sites and studied the dynamics of this event and the underlying ultrastructure. Most notable was the selective recruitment of ER membranes around lipid droplets where structural proteins and the viral replicase colocalize. Moreover, ER membranes wrapping lipid droplets were decorated with double membrane vesicles, providing a topological map of how HCV might coordinate the steps of viral replication and virion assembly. : Lee et al. visualized likely HCV assembly in live cells and with high resolution. During assembly, HCV structural proteins relocalize to the viral replicase and together induce the wrapping of lipid droplets by ER membranes. These membranes are linked to the viral replication organelle, allowing spatial coordination of replication and assembly. Keywords: replication organelle, double-membrane vesicles, correlative light and electron microscopy, CLEM, HCV, lipid metabolism, virus–host interaction, assembly, lipid droplet, plus-strand RNA virus
    Schlagwörter Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2019-06-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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