LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 4 of total 4

Search options

  1. Article ; Online: Lyssavirus matrix protein cooperates with phosphoprotein to modulate the Jak-Stat pathway.

    Sonthonnax, Florian / Besson, Benoit / Bonnaud, Emilie / Jouvion, Grégory / Merino, David / Larrous, Florence / Bourhy, Hervé

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 12171

    Abstract: Phosphoprotein (P) and matrix protein (M) cooperate to undermine the immune response to rabies virus (RABV) infections. While P is involved in the modulation of the Jak-Stat pathway through the cytoplasmic retention of interferon (IFN)-activated STAT1 ( ... ...

    Abstract Phosphoprotein (P) and matrix protein (M) cooperate to undermine the immune response to rabies virus (RABV) infections. While P is involved in the modulation of the Jak-Stat pathway through the cytoplasmic retention of interferon (IFN)-activated STAT1 (pSTAT1), M interacts with the RelAp43-p105-ABIN2-TPL2 complex, to efficiently inhibit the nuclear factor-κB (NF-κB) pathway. Using transfections, protein-complementation assays, reverse genetics and DNA ChIP, we identified a role of M protein in the control of Jak-Stat signaling pathway, in synergy with the P protein. In unstimulated cells, both M and P proteins were found to interact with JAK1. Upon type-I IFN stimulation, the M switches toward pSTAT1 interaction, which results in an enhanced capacity of P protein to interact with pSTAT1 and restrain it in the cytoplasm. Furthermore, the role for M-protein positions 77, 100, 104 and 110 was also demonstrated in interaction with both JAK1 and pY-STAT1, and confirmed in vivo. Together, these data indicate that M protein cooperates with P protein to restrain in parallel, and sequentially, NF-κB and Jak-Stat pathways.
    MeSH term(s) Animals ; Cytoplasm/metabolism ; HeLa Cells ; Humans ; Immunity, Innate ; Interferon Type I/metabolism ; Janus Kinase 1/metabolism ; Lyssavirus/metabolism ; Lyssavirus/pathogenicity ; Mice ; Mice, Inbred BALB C ; Mutagenesis, Site-Directed ; NF-kappa B/metabolism ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Promoter Regions, Genetic ; STAT1 Transcription Factor/genetics ; STAT1 Transcription Factor/metabolism ; Signal Transduction ; Th2 Cells/immunology ; Th2 Cells/metabolism ; Viral Matrix Proteins/genetics ; Viral Matrix Proteins/metabolism ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virulence
    Chemical Substances Interferon Type I ; NF-kappa B ; Phosphoproteins ; STAT1 Transcription Factor ; STAT1 protein, human ; Viral Matrix Proteins ; Viral Proteins ; JAK1 protein, human (EC 2.7.10.2) ; Janus Kinase 1 (EC 2.7.10.2)
    Language English
    Publishing date 2019-08-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-48507-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: A combination of two human monoclonal antibodies cures symptomatic rabies.

    de Melo, Guilherme Dias / Sonthonnax, Florian / Lepousez, Gabriel / Jouvion, Grégory / Minola, Andrea / Zatta, Fabrizia / Larrous, Florence / Kergoat, Lauriane / Mazo, Camille / Moigneu, Carine / Aiello, Roberta / Salomoni, Angela / Brisebard, Elise / De Benedictis, Paola / Corti, Davide / Bourhy, Hervé

    EMBO molecular medicine

    2020  Volume 12, Issue 11, Page(s) e12628

    Abstract: Rabies is a neglected disease caused by a neurotropic Lyssavirus, transmitted to humans predominantly by the bite of infected dogs. Rabies is preventable with vaccines or proper post-exposure prophylaxis (PEP), but it still causes about 60,000 deaths ... ...

    Abstract Rabies is a neglected disease caused by a neurotropic Lyssavirus, transmitted to humans predominantly by the bite of infected dogs. Rabies is preventable with vaccines or proper post-exposure prophylaxis (PEP), but it still causes about 60,000 deaths every year. No cure exists after the onset of clinical signs, and the case-fatality rate approaches 100% even with advanced supportive care. Here, we report that a combination of two potent neutralizing human monoclonal antibodies directed against the viral envelope glycoprotein cures symptomatic rabid mice. Treatment efficacy requires the concomitant administration of antibodies in the periphery and in the central nervous system through intracerebroventricular infusion. After such treatment, recovered mice presented good clinical condition, viral loads were undetectable, and the brain inflammatory profile was almost normal. Our findings provide the unprecedented proof of concept of an antibody-based therapeutic approach for symptomatic rabies.
    MeSH term(s) Animals ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing ; Antibodies, Viral ; Dogs ; Humans ; Lyssavirus ; Mice ; Post-Exposure Prophylaxis ; Rabies/drug therapy ; Rabies Vaccines ; Rabies virus
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Rabies Vaccines
    Language English
    Publishing date 2020-09-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2467145-9
    ISSN 1757-4684 ; 1757-4676
    ISSN (online) 1757-4684
    ISSN 1757-4676
    DOI 10.15252/emmm.202012628
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6784: 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)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity.

    Ben Khalifa, Youcef / Luco, Sophie / Besson, Benoit / Sonthonnax, Florian / Archambaud, Medhi / Grimes, Jonathan M / Larrous, Florence / Bourhy, Hervé

    Scientific reports

    2016  Volume 6, Page(s) 39420

    Abstract: The matrix (M) protein of wild isolates of rabies virus such as Tha (M-Tha) was previously shown to be able to interact with RelAp43, a protein of the NF-κB family, and to efficiently suppress NF-κB-dependent reporter gene expression, in contrast with ... ...

    Abstract The matrix (M) protein of wild isolates of rabies virus such as Tha (M-Tha) was previously shown to be able to interact with RelAp43, a protein of the NF-κB family, and to efficiently suppress NF-κB-dependent reporter gene expression, in contrast with the vaccine strain SAD. Here, we analyze the mechanisms involved in RelAp43-M protein interaction. We demonstrate that the central part of M-Tha, and the specific C-terminal region of RelAp43 are required for this interaction. Four differences in the corresponding amino acid sequences of the M-Tha and M-SAD are shown to be crucial for RelAp43 interaction and subsequent modulation of innate immune response. Furthermore, the capacity of M-Tha to interact with RelAp43 was shown to be crucial for the control of the expression of four genes (IFN, TNF, IL8 and CXCL2) during viral infection. These findings reveal that RelAp43 is a potent regulator of transcription of genes involved in innate immune response during rabies virus infection and that the M protein of wild isolates of rabies virus is a viral immune-modulatory factor playing an important role in this RelAp43-mediated host innate immunity response in contrast to M protein of vaccine strains, which have lost this property.
    MeSH term(s) Animals ; Cell Line ; Cell Line, Tumor ; Gene Expression/immunology ; HEK293 Cells ; HeLa Cells ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate/immunology ; Mice, Inbred BALB C ; NF-kappa B/metabolism ; Rabies/immunology ; Rabies/metabolism ; Rabies/virology ; Rabies virus/immunology ; Rabies virus/metabolism ; Viral Proteins/metabolism
    Chemical Substances NF-kappa B ; Viral Proteins
    Language English
    Publishing date 2016-12-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep39420
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Regulation of NF-κB by the p105-ABIN2-TPL2 complex and RelAp43 during rabies virus infection.

    Besson, Benoit / Sonthonnax, Florian / Duchateau, Magalie / Ben Khalifa, Youcef / Larrous, Florence / Eun, Hyeju / Hourdel, Véronique / Matondo, Mariette / Chamot-Rooke, Julia / Grailhe, Regis / Bourhy, Hervé

    PLoS pathogens

    2017  Volume 13, Issue 10, Page(s) e1006697

    Abstract: At the crossroad between the NF-κB and the MAPK pathways, the ternary complex composed of p105, ABIN2 and TPL2 is essential for the host cell response to pathogens. The matrix protein (M) of field isolates of rabies virus was previously shown to disturb ... ...

    Abstract At the crossroad between the NF-κB and the MAPK pathways, the ternary complex composed of p105, ABIN2 and TPL2 is essential for the host cell response to pathogens. The matrix protein (M) of field isolates of rabies virus was previously shown to disturb the signaling induced by RelAp43, a NF-κB protein close to RelA/p65. Here, we investigated how the M protein disturbs the NF-κB pathway in a RelAp43-dependant manner and the potential involvement of the ternary complex in this mechanism. Using a tandem affinity purification coupled with mass spectrometry approach, we show that RelAp43 interacts with the p105-ABIN2-TPL2 complex and we observe a strong perturbation of this complex in presence of M protein. M protein interaction with RelAp43 is associated with a wide disturbance of NF-κB signaling, involving a modulation of IκBα-, IκBβ-, and IκBε-RelAp43 interaction and a favored interaction of RelAp43 with the non-canonical pathway (RelB and p100/p52). Monitoring the interactions between host and viral proteins using protein-fragment complementation assay and bioluminescent resonance energy transfer, we further show that RelAp43 is associated to the p105-ABIN2-TPL2 complex as RelAp43-p105 interaction stabilizes the formation of a complex with ABIN2 and TPL2. Interestingly, the M protein interacts not only with RelAp43 but also with TPL2 and ABIN2. Upon interaction with this complex, M protein promotes the release of ABIN2, which ultimately favors the production of RelAp43-p50 NF-κB dimers. The use of recombinant rabies viruses further indicates that this mechanism leads to the control of IFNβ, TNF and CXCL2 expression during the infection and a high pathogenicity profile in rabies virus infected mice. All together, our results demonstrate the important role of RelAp43 and M protein in the regulation of NF-κB signaling.
    Language English
    Publishing date 2017-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1006697
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top