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Article ; Online: Interféron de type I et sélectivité de l’infection des cellules du système nerveux central par le virus de la rougeole.

Ferren, Marion / Horvat, Branka / Gerlier, Denis / Mathieu, Cyrille

2021 Volume 37, Issue 1, Page(s) 22–25

Title translation	Type I interferon and selective permissiveness of central nervous system to measles virus infection.
MeSH term(s)	Animals ; Antigens, Viral/analysis ; Brain/immunology ; Central Nervous System Viral Diseases/virology ; Dendritic Cells/virology ; Encephalitis, Viral/virology ; Humans ; Interferon Type I/metabolism ; Macrophages, Alveolar/virology ; Measles virus/immunology ; Mice ; Mice, Transgenic/metabolism ; Receptor, Interferon alpha-beta/deficiency ; Receptor, Interferon alpha-beta/genetics ; Signaling Lymphocytic Activation Molecule Family Member 1/metabolism ; Virus Internalization
Chemical Substances	Antigens, Viral ; Interferon Type I ; Slamf1 protein, mouse ; Receptor, Interferon alpha-beta (156986-95-7) ; Signaling Lymphocytic Activation Molecule Family Member 1 (169535-43-7)
Language	French
Publishing date	2021-01-25
Publishing country	France
Document type	News ; Research Support, Non-U.S. Gov't
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/2020252
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Article ; Online: Early Permissiveness of Central Nervous System Cells to Measles Virus Infection Is Determined by Hyperfusogenicity and Interferon Pressure.

Ferren, Marion / Lalande, Alexandre / Iampietro, Mathieu / Canus, Lola / Decimo, Didier / Gerlier, Denis / Porotto, Matteo / Mathieu, Cyrille

Viruses

2023 Volume 15, Issue 1

Abstract: The cessation of measles virus (MeV) vaccination in more than 40 countries as a consequence of the COVID-19 pandemic is expected to significantly increase deaths due to measles. MeV can infect the central nervous system (CNS) and lead to lethal ... ...

Abstract	The cessation of measles virus (MeV) vaccination in more than 40 countries as a consequence of the COVID-19 pandemic is expected to significantly increase deaths due to measles. MeV can infect the central nervous system (CNS) and lead to lethal encephalitis. Substantial part of virus sequences recovered from patients' brain were mutated in the matrix and/or the fusion protein (F). Mutations of the heptad repeat domain located in the C terminal (HRC) part of the F protein were often observed and were associated to hyperfusogenicity. These mutations promote brain invasion as a hallmark of neuroadaptation. Wild-type F allows entry into the brain, followed by limited spreading compared with the massive invasion observed for hyperfusogenic MeV. Taking advantage of our ex vivo models of hamster organotypic brain cultures, we investigated how the hyperfusogenic mutations in the F HRC domain modulate virus distribution in CNS cells. In this study, we also identified the dependence of neural cells susceptibility on both their activation state and destabilization of the virus F protein. Type I interferon (IFN-I) impaired mainly astrocytes and microglial cells permissiveness contrarily to neurons, opening a new way of consideration on the development of treatments against viral encephalitis.
MeSH term(s)	Animals ; Cricetinae ; Humans ; Brain ; Central Nervous System/virology ; Interferons/metabolism ; Measles ; Measles virus/physiology ; Viral Fusion Proteins/genetics
Chemical Substances	Interferons (9008-11-1) ; Viral Fusion Proteins
Language	English
Publishing date	2023-01-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; 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/v15010229
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Measles Encephalitis: Towards New Therapeutics.

Ferren, Marion / Horvat, Branka / Mathieu, Cyrille

Viruses

2019 Volume 11, Issue 11

Abstract: Measles remains a major cause of morbidity and mortality worldwide among vaccine preventable diseases. Recent decline in vaccination coverage resulted in re-emergence of measles outbreaks. Measles virus (MeV) infection causes an acute systemic disease, ... ...

Abstract	Measles remains a major cause of morbidity and mortality worldwide among vaccine preventable diseases. Recent decline in vaccination coverage resulted in re-emergence of measles outbreaks. Measles virus (MeV) infection causes an acute systemic disease, associated in certain cases with central nervous system (CNS) infection leading to lethal neurological disease. Early following MeV infection some patients develop acute post-infectious measles encephalitis (APME), which is not associated with direct infection of the brain. MeV can also infect the CNS and cause sub-acute sclerosing panencephalitis (SSPE) in immunocompetent people or measles inclusion-body encephalitis (MIBE) in immunocompromised patients. To date, cellular and molecular mechanisms governing CNS invasion are still poorly understood. Moreover, the known MeV entry receptors are not expressed in the CNS and how MeV enters and spreads in the brain is not fully understood. Different antiviral treatments have been tested and validated in vitro, ex vivo and in vivo
MeSH term(s)	Animals ; Antiviral Agents/therapeutic use ; Central Nervous System/pathology ; Central Nervous System/virology ; Disease Models, Animal ; Encephalitis, Viral/drug therapy ; Encephalitis, Viral/epidemiology ; Encephalitis, Viral/pathology ; Encephalitis, Viral/virology ; Humans ; Measles/drug therapy ; Measles/epidemiology ; Measles/pathology ; Measles/virology ; Measles virus/pathogenicity ; Measles virus/physiology ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Viral Tropism
Chemical Substances	Antiviral Agents ; Viral Proteins
Language	English
Publishing date	2019-11-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v11111017
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Article: Measles Encephalitis: Towards New Therapeutics

Ferren, Marion / Horvat, Branka / Mathieu, Cyrille

Viruses. 2019 Nov. 02, v. 11, no. 11

2019

Abstract	Measles remains a major cause of morbidity and mortality worldwide among vaccine preventable diseases. Recent decline in vaccination coverage resulted in re-emergence of measles outbreaks. Measles virus (MeV) infection causes an acute systemic disease, associated in certain cases with central nervous system (CNS) infection leading to lethal neurological disease. Early following MeV infection some patients develop acute post-infectious measles encephalitis (APME), which is not associated with direct infection of the brain. MeV can also infect the CNS and cause sub-acute sclerosing panencephalitis (SSPE) in immunocompetent people or measles inclusion-body encephalitis (MIBE) in immunocompromised patients. To date, cellular and molecular mechanisms governing CNS invasion are still poorly understood. Moreover, the known MeV entry receptors are not expressed in the CNS and how MeV enters and spreads in the brain is not fully understood. Different antiviral treatments have been tested and validated in vitro, ex vivo and in vivo, mainly in small animal models. Most treatments have high efficacy at preventing infection but their effectiveness after CNS manifestations remains to be evaluated. This review describes MeV neural infection and current most advanced therapeutic approaches potentially applicable to treat MeV CNS infection.
Keywords	Measles morbillivirus ; animal models ; brain ; encephalitis ; measles ; morbidity ; mortality ; patients ; receptors ; vaccination ; vaccines
Language	English
Dates of publication	2019-1102
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v11111017
Database	NAL-Catalogue (AGRICOLA)

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Article: Hamster organotypic kidney culture model of early-stage SARS-CoV-2 infection highlights a two-step renal susceptibility.

Shyfrin, Sophie R / Ferren, Marion / Perrin-Cocon, Laure / Espi, Maxime / Charmetant, Xavier / Brailly, Manon / Decimo, Didier / Iampietro, Mathieu / Canus, Lola / Horvat, Branka / Lotteau, Vincent / Vidalain, Pierre-Olivier / Thaunat, Olivier / Mathieu, Cyrille

Journal of tissue engineering

2022 Volume 13, Page(s) 20417314221122130

Abstract: Kidney pathology is frequently reported in patients hospitalized with COVID-19, the pandemic disease caused by the Severe acute respiratory coronavirus 2 (SARS-CoV-2). However, due to a lack of suitable study models, the events occurring in the kidney ... ...

Abstract	Kidney pathology is frequently reported in patients hospitalized with COVID-19, the pandemic disease caused by the Severe acute respiratory coronavirus 2 (SARS-CoV-2). However, due to a lack of suitable study models, the events occurring in the kidney during the earliest stages of infection remain unknown. We have developed hamster organotypic kidney cultures (OKCs) to study the early stages of direct renal infection. OKCs maintained key renal structures in their native three-dimensional arrangement. SARS-CoV-2 productively replicated in hamster OKCs, initially targeting endothelial cells and later disseminating into proximal tubules. We observed a delayed interferon response, markers of necroptosis and pyroptosis, and an early repression of pro-inflammatory cytokines transcription followed by a strong later upregulation. While it remains an open question whether an active replication of SARS-CoV-2 takes place in the kidneys of COVID-19 patients with AKI, our model provides new insights into the kinetics of SARS-CoV-2 kidney infection and can serve as a powerful tool for studying kidney infection by other pathogens and testing the renal toxicity of drugs.
Language	English
Publishing date	2022-09-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2573915-3
ISSN	2041-7314
ISSN	2041-7314
DOI	10.1177/20417314221122130
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Article ; Online: Hamster organotypic modeling of SARS-CoV-2 lung and brainstem infection.

Ferren, Marion / Favède, Valérie / Decimo, Didier / Iampietro, Mathieu / Lieberman, Nicole A P / Weickert, Jean-Luc / Pelissier, Rodolphe / Mazelier, Magalie / Terrier, Olivier / Moscona, Anne / Porotto, Matteo / Greninger, Alexander L / Messaddeq, Nadia / Horvat, Branka / Mathieu, Cyrille

Nature communications

2021 Volume 12, Issue 1, Page(s) 5809

Abstract: SARS-CoV-2 has caused a global pandemic of COVID-19 since its emergence in December 2019. The infection causes a severe acute respiratory syndrome and may also spread to central nervous system leading to neurological sequelae. We have developed and ... ...

Abstract	SARS-CoV-2 has caused a global pandemic of COVID-19 since its emergence in December 2019. The infection causes a severe acute respiratory syndrome and may also spread to central nervous system leading to neurological sequelae. We have developed and characterized two new organotypic cultures from hamster brainstem and lung tissues that offer a unique opportunity to study the early steps of viral infection and screening antivirals. These models are not dedicated to investigate how the virus reaches the brain. However, they allow validating the early tropism of the virus in the lungs and demonstrating that SARS-CoV-2 could infect the brainstem and the cerebellum, mainly by targeting granular neurons. Viral infection induces specific interferon and innate immune responses with patterns specific to each organ, along with cell death by apoptosis, necroptosis, and pyroptosis. Overall, our data illustrate the potential of rapid modeling of complex tissue-level interactions during infection by a newly emerged virus.
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/pharmacology ; Alanine/analogs & derivatives ; Alanine/pharmacology ; Alveolar Epithelial Cells/virology ; Animals ; Antiviral Agents/pharmacology ; Brain Stem/cytology ; Brain Stem/immunology ; Brain Stem/pathology ; Brain Stem/virology ; Cricetinae ; Immunity, Innate ; Inflammation ; Lung/cytology ; Lung/immunology ; Lung/pathology ; Lung/virology ; Models, Biological ; Neurons/virology ; Organ Culture Techniques ; Regulated Cell Death ; SARS-CoV-2/drug effects ; SARS-CoV-2/pathogenicity ; Viral Tropism
Chemical Substances	Antiviral Agents ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX)
Language	English
Publishing date	2021-10-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-26096-z
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Article ; Online: Single-chain variable fragment antibody constructs neutralize measles virus infection in vitro and in vivo.

Mathieu, Cyrille / Ferren, Marion / Harder, Olivia / Bovier, Francesca T / Marcink, Tara C / Predella, Camilla / Angius, Fabrizio / Drew-Bear, Jennifer / Dorrello, N Valerio / Greninger, Alex L / Moscona, Anne / Niewiesk, Stefan / Horvat, Branka / Porotto, Matteo

Cellular & molecular immunology

2021 Volume 18, Issue 7, Page(s) 1835–1837

MeSH term(s)	Antibodies, Viral ; Humans ; Measles ; Measles virus ; Single-Chain Antibodies
Chemical Substances	Antibodies, Viral ; Single-Chain Antibodies
Language	English
Publishing date	2021-05-18
Publishing country	China
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2435097-7
ISSN	2042-0226 ; 1672-7681
ISSN (online)	2042-0226
ISSN	1672-7681
DOI	10.1038/s41423-021-00691-y
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Article ; Online: Activation of cGAS/STING pathway upon paramyxovirus infection.

Iampietro, Mathieu / Dumont, Claire / Mathieu, Cyrille / Spanier, Julia / Robert, Jonathan / Charpenay, Aude / Dupichaud, Sébastien / Dhondt, Kévin P / Aurine, Noémie / Pelissier, Rodolphe / Ferren, Marion / Mély, Stéphane / Gerlier, Denis / Kalinke, Ulrich / Horvat, Branka

iScience

2021 Volume 24, Issue 6, Page(s) 102519

Abstract: During inflammatory diseases, cancer, and infection, the cGAS/STING pathway is known to recognize foreign or self-DNA in the cytosol and activate an innate immune response. Here, we report that negative-strand RNA paramyxoviruses, Nipah virus (NiV), and ... ...

Abstract	During inflammatory diseases, cancer, and infection, the cGAS/STING pathway is known to recognize foreign or self-DNA in the cytosol and activate an innate immune response. Here, we report that negative-strand RNA paramyxoviruses, Nipah virus (NiV), and measles virus (MeV), can also trigger the cGAS/STING axis. Although mice deficient for MyD88, TRIF, and MAVS still moderately control NiV infection when compared with wild-type mice, additional STING deficiency resulted in 100% lethality, suggesting synergistic roles of these pathways in host protection. Moreover, deletion of cGAS or STING resulted in decreased type I interferon production with enhanced paramyxoviral infection in both human and murine cells. Finally, the phosphorylation and ubiquitination of STING, observed during viral infections, confirmed the activation of cGAS/STING pathway by NiV and MeV. Our data suggest that cGAS/STING activation is critical in controlling paramyxovirus infection and possibly represents attractive targets to develop countermeasures against severe disease induced by these pathogens.
Language	English
Publishing date	2021-05-07
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2021.102519
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Article ; Online: Molecular Features of the Measles Virus Viral Fusion Complex That Favor Infection and Spread in the Brain.

Mathieu, Cyrille / Bovier, Francesca T / Ferren, Marion / Lieberman, Nicole A P / Predella, Camilla / Lalande, Alexandre / Peddu, Vikas / Lin, Michelle J / Addetia, Amin / Patel, Achchhe / Outlaw, Victor / Corneo, Barbara / Dorrello, N Valerio / Briese, Thomas / Hardie, Diana / Horvat, Branka / Moscona, Anne / Greninger, Alexander L / Porotto, Matteo

mBio

2021 Volume 12, Issue 3, Page(s) e0079921

Abstract: Measles virus (MeV) bearing a single amino acid change in the fusion protein (F)-L454W-was isolated from two patients who died of MeV central nervous system (CNS) infection. This mutation in F confers an advantage over wild-type virus in the CNS, ... ...

Abstract	Measles virus (MeV) bearing a single amino acid change in the fusion protein (F)-L454W-was isolated from two patients who died of MeV central nervous system (CNS) infection. This mutation in F confers an advantage over wild-type virus in the CNS, contributing to disease in these patients. Using murine
MeSH term(s)	Amino Acid Substitution ; Animals ; Brain/cytology ; Brain/pathology ; Brain/virology ; Central Nervous System Diseases/virology ; Chlorocebus aethiops ; Female ; HEK293 Cells ; Humans ; Induced Pluripotent Stem Cells/pathology ; Induced Pluripotent Stem Cells/virology ; Male ; Measles/virology ; Measles virus/genetics ; Measles virus/pathogenicity ; Metagenomics ; Mice ; Neurons/virology ; Organoids/cytology ; Organoids/virology ; Vero Cells ; Viral Fusion Proteins/chemistry ; Viral Fusion Proteins/classification ; Viral Fusion Proteins/genetics ; Viral Fusion Proteins/metabolism
Chemical Substances	Viral Fusion Proteins
Language	English
Publishing date	2021-06-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.00799-21
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Article: Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection.

Research square

2022

Abstract: Measles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitors, derived from heptad-repeat regions of the measles virus (MeV) ... ...

Abstract	Measles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitors, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, block respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We used a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptides to the respiratory tract and demonstrated the absence of adverse effects and lung pathology in macaques. The nebulized peptide efficiently prevented MeV infection, resulting in the complete absence of MeV RNA, MeV-infected cells, and MeV-specific humoral responses in treated animals. This strategy provides an additional shield which complements vaccination to fight against respiratory infection, presenting a proof-of-concept for the aerosol delivery of fusion inhibitory peptides to protect against measles and other airborne viruses, including SARS-CoV-2, in case of high-risk exposure, that can be readily translated to human trials.
Language	English
Publishing date	2022-06-01
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-1700877/v1
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