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  1. Book ; Online ; E-Book: Antiviral discovery for highly pathogenic emerging viruses

    Muñoz-Fontela, César / Delgado, Rafael

    (Drug discovery series ; no. 80)

    2022  

    Author's details edited by César Muñoz-Fontela and Rafael Delgado
    Series title Drug discovery series ; no. 80
    RSC drug discovery series
    Collection RSC drug discovery series
    Keywords Arzneimittelforschung ; Viruzid
    Subject Antiviraler Wirkstoff ; Antivirales Agens ; Pharmaforschung ; Arzneimittel ; Wirkstoffforschung ; Arzneistoffforschung ; Drug discovery
    Language English
    Size 1 Online-Ressource (xvii, 290 Seiten), Illustrationen
    Publisher Royal Society of Chemistry
    Publishing place London
    Publishing country Great Britain
    Document type Book ; Online ; E-Book
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    HBZ-ID HT021249642
    ISBN 978-1-83916-053-0 ; 978-1-78801-685-8 ; 9781788015646 ; 1-83916-053-5 ; 1-78801-685-8 ; 1788015649
    DOI 10.1039/9781788016858
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: Animal Model Alternatives in Filovirus and Bornavirus Research.

    Widerspick, Lina / Steffen, Johanna Friederike / Tappe, Dennis / Muñoz-Fontela, César

    Viruses

    2023  Volume 15, Issue 1

    Abstract: ... The ... ...

    Abstract The order
    MeSH term(s) Animals ; Humans ; Filoviridae ; Bornaviridae/genetics ; Models, Animal
    Language English
    Publishing date 2023-01-04
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v15010158
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Use of Hu-PBL Mice to Study Pathogenesis of Human-Restricted Viruses.

    Brunetti, Jesús Emanuel / Kitsera, Maksym / Muñoz-Fontela, César / Rodríguez, Estefanía

    Viruses

    2023  Volume 15, Issue 1

    Abstract: Different humanized mouse models have been developed to study human diseases such as autoimmune illnesses, cancer and viral infections. These models are based on the use of immunodeficient mouse strains that are transplanted with human tissues or human ... ...

    Abstract Different humanized mouse models have been developed to study human diseases such as autoimmune illnesses, cancer and viral infections. These models are based on the use of immunodeficient mouse strains that are transplanted with human tissues or human immune cells. Among the latter, mice transplanted with hematopoietic stem cells have been widely used to study human infectious diseases. However, mouse models built upon the transplantation of donor-specific mature immune cells are still under development, especially in the field of viral infections. These models can retain the unique immune memory of the donor, making them suitable for the study of correlates of protection upon natural infection or vaccination. Here, we will review some of these models and how they have been applied to virology research. Moreover, the future applications and the potential of these models to design therapies against human viral infections are discussed.
    MeSH term(s) Mice ; Humans ; Animals ; Mice, SCID ; Disease Models, Animal ; Viruses/genetics
    Language English
    Publishing date 2023-01-13
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v15010228
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Role of Type I Interferons on Filovirus Pathogenesis.

    Escudero-Pérez, Beatriz / Muñoz-Fontela, César

    Vaccines

    2019  Volume 7, Issue 1

    Abstract: Filoviruses, such as Ebola and Marburg virus, encode viral proteins with the ability to counteract the type I interferon (IFN-I) response. These IFN-I antagonist proteins are crucial to ensure virus replication, prevent an antiviral state in infected and ...

    Abstract Filoviruses, such as Ebola and Marburg virus, encode viral proteins with the ability to counteract the type I interferon (IFN-I) response. These IFN-I antagonist proteins are crucial to ensure virus replication, prevent an antiviral state in infected and bystander cells, and impair the ability of antigen-presenting cells to initiate adaptive immune responses. However, in recent years, a number of studies have underscored the conflicting data between in vitro studies and in vivo data obtained in animal models and clinical studies during outbreaks. This review aims to summarize these data and to discuss the relative contributions of IFN-α and IFN-β to filovirus pathogenesis in animal models and humans. Finally, we evaluate the putative utilization of IFN-I in post-exposure therapy and its implications as a biomarker of vaccine efficacy.
    Language English
    Publishing date 2019-02-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines7010022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Role of Type I Interferons on Filovirus Pathogenesis

    Beatriz Escudero-Pérez / César Muñoz-Fontela

    Vaccines, Vol 7, Iss 1, p

    2019  Volume 22

    Abstract: Filoviruses, such as Ebola and Marburg virus, encode viral proteins with the ability to counteract the type I interferon (IFN-I) response. These IFN-I antagonist proteins are crucial to ensure virus replication, prevent an antiviral state in infected and ...

    Abstract Filoviruses, such as Ebola and Marburg virus, encode viral proteins with the ability to counteract the type I interferon (IFN-I) response. These IFN-I antagonist proteins are crucial to ensure virus replication, prevent an antiviral state in infected and bystander cells, and impair the ability of antigen-presenting cells to initiate adaptive immune responses. However, in recent years, a number of studies have underscored the conflicting data between in vitro studies and in vivo data obtained in animal models and clinical studies during outbreaks. This review aims to summarize these data and to discuss the relative contributions of IFN-α and IFN-β to filovirus pathogenesis in animal models and humans. Finally, we evaluate the putative utilization of IFN-I in post-exposure therapy and its implications as a biomarker of vaccine efficacy.
    Keywords Interferon ; filovirus ; immune responses ; pathogenicity ; Medicine ; R
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Ebola Virus Disease in Humans: Pathophysiology and Immunity.

    Muñoz-Fontela, César / McElroy, Anita K

    Current topics in microbiology and immunology

    2017  Volume 411, Page(s) 141–169

    Abstract: Viruses of the Ebolavirus genus cause sporadic epidemics of severe and systemic febrile disease that are fueled by human-to-human transmission. Despite the notoriety of ebolaviruses, particularly Ebola virus (EBOV), as prominent viral hemorrhagic fever ... ...

    Abstract Viruses of the Ebolavirus genus cause sporadic epidemics of severe and systemic febrile disease that are fueled by human-to-human transmission. Despite the notoriety of ebolaviruses, particularly Ebola virus (EBOV), as prominent viral hemorrhagic fever agents, and the international concern regarding Ebola virus disease (EVD) outbreaks, very little is known about the pathophysiology of EVD in humans and, in particular, about the human immune correlates of survival and immune memory. This lack of basic knowledge about physiological characteristics of EVD is probably attributable to the dearth of clinical and laboratory data gathered from past outbreaks. The unprecedented magnitude of the EVD epidemic that occurred in West Africa from 2013 to 2016 has allowed, for the first time, evaluation of clinical, epidemiological, and immunological parameters in a significant number of patients using state-of-the-art laboratory equipment. This review will summarize the data from the literature regarding human pathophysiologic and immunologic responses to filoviral infection.
    MeSH term(s) Africa, Western/epidemiology ; Disease Outbreaks ; Ebolavirus/immunology ; Hemorrhagic Fever, Ebola/epidemiology ; Hemorrhagic Fever, Ebola/immunology ; Hemorrhagic Fever, Ebola/physiopathology ; Hemorrhagic Fever, Ebola/virology ; Humans
    Keywords covid19
    Language English
    Publishing date 2017-06-28
    Publishing country Germany
    Document type Journal Article ; Review
    ISSN 0070-217X
    ISSN 0070-217X
    DOI 10.1007/82_2017_11
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Book ; Online ; Thesis: Contributions of NP isoforms to the regulation of the Junín virus replication cycle and interactions with the host cell

    Bostedt, Linus Verfasser] / [Groseth, Allison [Akademischer Betreuer] / Mettenleiter, Thomas C. [Akademischer Betreuer] / Mettenleiter, Thomas C. [Gutachter] / Muñoz-Fontela, César [Gutachter]

    2023  

    Author's details Linus Bostedt ; Gutachter: Thomas C. Mettenleiter, César Muñoz-Fontela ; Allison Groseth, Thomas C. Mettenleiter
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Universität Greifswald
    Publishing place Greifswald
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  8. Article ; Online: Immune barriers of Ebola virus infection.

    McElroy, Anita K / Mühlberger, Elke / Muñoz-Fontela, César

    Current opinion in virology

    2018  Volume 28, Page(s) 152–160

    Abstract: Since its initial emergence in 1976 in northern Democratic Republic of Congo (DRC), Ebola virus (EBOV) has been a global health concern due to its virulence in humans, the mystery surrounding the identity of its host reservoir and the unpredictable ... ...

    Abstract Since its initial emergence in 1976 in northern Democratic Republic of Congo (DRC), Ebola virus (EBOV) has been a global health concern due to its virulence in humans, the mystery surrounding the identity of its host reservoir and the unpredictable nature of Ebola virus disease (EVD) outbreaks. Early after the first clinical descriptions of a disease resembling a 'septic-shock-like syndrome', with coagulation abnormalities and multi-system organ failure, researchers began to evaluate the role of the host immune response in EVD pathophysiology. In this review, we summarize how data gathered during the last 40 years in the laboratory as well as in the field have provided insight into EBOV immunity. From molecular mechanisms involved in EBOV recognition in infected cells, to antigen processing and adaptive immune responses, we discuss current knowledge on the main immune barriers of infection as well as outstanding research questions.
    MeSH term(s) Adaptive Immunity ; Animals ; Antigen Presentation/immunology ; Disease Models, Animal ; Disease Outbreaks ; Ebolavirus/genetics ; Ebolavirus/immunology ; Ebolavirus/pathogenicity ; Hemorrhagic Fever, Ebola/immunology ; Hemorrhagic Fever, Ebola/physiopathology ; Host-Pathogen Interactions/immunology ; Humans ; Interferons/immunology ; Mice ; Virulence
    Chemical Substances Interferons (9008-11-1)
    Language English
    Publishing date 2018-02-16
    Publishing country Netherlands
    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. ; Review
    ZDB-ID 2611378-8
    ISSN 1879-6265 ; 1879-6257
    ISSN (online) 1879-6265
    ISSN 1879-6257
    DOI 10.1016/j.coviro.2018.01.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Quantification of Type I Interferon Inhibition by Viral Proteins: Ebola Virus as a Case Study.

    Locke, Macauley / Lythe, Grant / López-García, Martín / Muñoz-Fontela, César / Carroll, Miles / Molina-París, Carmen

    Viruses

    2021  Volume 13, Issue 12

    Abstract: Type I interferons (IFNs) are cytokines with both antiviral properties and protective roles in innate immune responses to viral infection. They induce an antiviral cellular state and link innate and adaptive immune responses. Yet, viruses have evolved ... ...

    Abstract Type I interferons (IFNs) are cytokines with both antiviral properties and protective roles in innate immune responses to viral infection. They induce an antiviral cellular state and link innate and adaptive immune responses. Yet, viruses have evolved different strategies to inhibit such host responses. One of them is the existence of viral proteins which subvert type I IFN responses to allow quick and successful viral replication, thus, sustaining the infection within a host. We propose mathematical models to characterise the intra-cellular mechanisms involved in viral protein antagonism of type I IFN responses, and compare three different molecular inhibition strategies. We study the Ebola viral protein, VP35, with this mathematical approach. Approximate Bayesian computation sequential Monte Carlo, together with experimental data and the mathematical models proposed, are used to perform model calibration, as well as model selection of the different hypotheses considered. Finally, we assess if model parameters are identifiable and discuss how such identifiability can be improved with new experimental data.
    MeSH term(s) Animals ; Bayes Theorem ; Ebolavirus/pathogenicity ; Ebolavirus/physiology ; Hemorrhagic Fever, Ebola/immunology ; Hemorrhagic Fever, Ebola/virology ; Immunity, Innate ; Interferon Type I/antagonists & inhibitors ; Interferon Type I/metabolism ; Macaca mulatta ; Models, Biological ; Monte Carlo Method ; Viral Regulatory and Accessory Proteins/metabolism
    Chemical Substances Interferon Type I ; VP35 protein, filovirus ; Viral Regulatory and Accessory Proteins
    Language English
    Publishing date 2021-12-04
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13122441
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Potential pharmacological strategies targeting the Niemann-Pick C1 receptor and Ebola virus glycoprotein interaction.

    Morales-Tenorio, Marcos / Ginex, Tiziana / Cuesta-Geijo, Miguel Ángel / Campillo, Nuria E / Muñoz-Fontela, César / Alonso, Covadonga / Delgado, Rafael / Gil, Carmen

    European journal of medicinal chemistry

    2021  Volume 223, Page(s) 113654

    Abstract: Niemann-Pick C1 (NPC1) receptor is an intracellular protein located in late endosomes and lysosomes whose main function is to regulate intracellular cholesterol trafficking. Besides being postulated as necessary for the infection of highly pathogenic ... ...

    Abstract Niemann-Pick C1 (NPC1) receptor is an intracellular protein located in late endosomes and lysosomes whose main function is to regulate intracellular cholesterol trafficking. Besides being postulated as necessary for the infection of highly pathogenic viruses in which the integrity of cholesterol transport is required, this protein also allows the entry of the Ebola virus (EBOV) into the host cells acting as an intracellular receptor. EBOV glycoprotein (EBOV-GP) interaction with NPC1 at the endosomal membrane triggers the release of the viral material into the host cell, starting the infective cycle. Disruption of the NPC1/EBOV-GP interaction could represent an attractive strategy for the development of drugs aimed at inhibiting viral entry and thus infection. Some of the today available EBOV inhibitors were proposed to interrupt this interaction, but molecular and structural details about their mode of action are still preliminary thus more efforts are needed to properly address these points. Here, we provide a critical discussion of the potential of NPC1 and its interaction with EBOV-GP as a therapeutic target for viral infections.
    MeSH term(s) Antibodies/immunology ; Antibodies/pharmacology ; Ebolavirus/metabolism ; Glycoproteins/chemistry ; Glycoproteins/metabolism ; Hemorrhagic Fever, Ebola/drug therapy ; Hemorrhagic Fever, Ebola/pathology ; Humans ; Molecular Docking Simulation ; Niemann-Pick C1 Protein/chemistry ; Niemann-Pick C1 Protein/immunology ; Niemann-Pick C1 Protein/metabolism ; Protein Binding ; Small Molecule Libraries/chemistry ; Small Molecule Libraries/metabolism ; Small Molecule Libraries/pharmacology ; Small Molecule Libraries/therapeutic use ; Virus Internalization/drug effects
    Chemical Substances Antibodies ; Glycoproteins ; Niemann-Pick C1 Protein ; Small Molecule Libraries
    Language English
    Publishing date 2021-06-19
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 188597-2
    ISSN 1768-3254 ; 0009-4374 ; 0223-5234
    ISSN (online) 1768-3254
    ISSN 0009-4374 ; 0223-5234
    DOI 10.1016/j.ejmech.2021.113654
    Database MEDical Literature Analysis and Retrieval System OnLINE

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