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  1. Article ; Online: Regulation of Innate Immune Responses by Autophagy: A Goldmine for Viruses.

    Pradel, Baptiste / Robert-Hebmann, Véronique / Espert, Lucile

    Frontiers in immunology

    2020  Volume 11, Page(s) 578038

    Abstract: Autophagy is a lysosomal degradation pathway for intracellular components and is highly conserved across eukaryotes. This process is a key player in innate immunity and its activation has anti-microbial effects by directly targeting pathogens and also by ...

    Abstract Autophagy is a lysosomal degradation pathway for intracellular components and is highly conserved across eukaryotes. This process is a key player in innate immunity and its activation has anti-microbial effects by directly targeting pathogens and also by regulating innate immune responses. Autophagy dysfunction is often associated with inflammatory diseases. Many studies have shown that it can also play a role in the control of innate immunity by preventing exacerbated inflammation and its harmful effects toward the host. The arms race between hosts and pathogens has led some viruses to evolve strategies that enable them to benefit from autophagy, either by directly hijacking the autophagy pathway for their life cycle, or by using its regulatory functions in innate immunity. The control of viral replication and spread involves the production of anti-viral cytokines. Controlling the signals that lead to production of these cytokines is a perfect way for viruses to escape from innate immune responses and establish successful infection. Published reports related to this last viral strategy have extensively grown in recent years. In this review we describe several links between autophagy and regulation of innate immune responses and we provide an overview of how viruses exploit these links for their own benefit.
    MeSH term(s) Animals ; Antiviral Agents/pharmacology ; Autophagy/drug effects ; Autophagy-Related Proteins/metabolism ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/drug effects ; Inflammation Mediators ; Signal Transduction ; Viruses/drug effects ; Viruses/immunology ; Viruses/pathogenicity
    Chemical Substances Antiviral Agents ; Autophagy-Related Proteins ; Inflammation Mediators
    Keywords covid19
    Language English
    Publishing date 2020-10-06
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.578038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: LC3B conjugation machinery promotes autophagy-independent HIV-1 entry in CD4

    Pradel, Baptiste / Cantaloube, Guilhem / Villares, Marie / Deffieu, Maïka S / Robert-Hebmann, Véronique / Lucansky, Vincent / Faure, Mathias / Chazal, Nathalie / Gaudin, Raphaël / Espert, Lucile

    Autophagy

    2024  , Page(s) 1–12

    Abstract: HIV-1 entry into ... ...

    Abstract HIV-1 entry into CD4
    Language English
    Publishing date 2024-04-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2024.2338573
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Autophagy Nucleation Factor ATG9 Forms Nanoclusters with the HIV-1 Receptor DC-SIGN and Regulates Early Antiviral Autophagy in Human Dendritic Cells.

    Papin, Laure / Lehmann, Martin / Lagisquet, Justine / Maarifi, Ghizlane / Robert-Hebmann, Véronique / Mariller, Christophe / Guerardel, Yann / Espert, Lucile / Haucke, Volker / Blanchet, Fabien P

    International journal of molecular sciences

    2023  Volume 24, Issue 10

    Abstract: Dendritic cells (DC) are critical cellular mediators of host immunity, notably by expressing a broad panel of pattern recognition receptors. One of those receptors, the C-type lectin receptor DC-SIGN, was previously reported as a regulator of endo/ ... ...

    Abstract Dendritic cells (DC) are critical cellular mediators of host immunity, notably by expressing a broad panel of pattern recognition receptors. One of those receptors, the C-type lectin receptor DC-SIGN, was previously reported as a regulator of endo/lysosomal targeting through functional connections with the autophagy pathway. Here, we confirmed that DC-SIGN internalization intersects with LC3
    MeSH term(s) Humans ; HIV-1/physiology ; Antiviral Agents/metabolism ; Dendritic Cells ; Lectins, C-Type/metabolism ; Autophagy
    Chemical Substances DC-specific ICAM-3 grabbing nonintegrin ; Antiviral Agents ; Lectins, C-Type
    Language English
    Publishing date 2023-05-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24109008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: La phagocytose associée à LC3 (LAP) - Phagocytose ou autophagie ?

    Galais, Mathilde / Pradel, Baptiste / Vergne, Isabelle / Robert-Hebmann, Véronique / Espert, Lucile / Biard-Piechaczyk, Martine

    Medecine sciences : M/S

    2019  Volume 35, Issue 8-9, Page(s) 635–642

    Abstract: Phagocytosis and macroautophagy, named here autophagy, are two essential mechanisms of lysosomal degradation of diverse cargos into membrane structures. Both mechanisms are involved in immune regulation and cell survival. However, phagocytosis triggers ... ...

    Title translation LAP (LC3-associated phagocytosis): phagocytosis or autophagy?
    Abstract Phagocytosis and macroautophagy, named here autophagy, are two essential mechanisms of lysosomal degradation of diverse cargos into membrane structures. Both mechanisms are involved in immune regulation and cell survival. However, phagocytosis triggers degradation of extracellular material whereas autophagy engulfs only cytoplasmic elements. Furthermore, activation and maturation of these two processes are different. LAP (LC3-associated phagocytosis) is a form of phagocytosis that uses components of the autophagy pathway. It can eliminate (i) pathogens, (ii) immune complexes, (iii) threatening neighbouring cells, dead or alive, and (iv) cell debris, such as POS (photoreceptor outer segment) and the midbody released at the end of mitosis. Cells have thus optimized their means of elimination of dangerous components by sharing some fundamental elements coming from the two main lysosomal degradation pathways.
    MeSH term(s) Animals ; Autophagy/physiology ; Humans ; Immune Evasion/physiology ; Infections/immunology ; Infections/metabolism ; Infections/pathology ; Macrophages/immunology ; Microtubule-Associated Proteins/physiology ; Phagocytosis/physiology ; Phagosomes/immunology
    Chemical Substances MAP1LC3A protein, human ; Microtubule-Associated Proteins
    Language French
    Publishing date 2019-09-18
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 632733-3
    ISSN 1958-5381 ; 0767-0974
    ISSN (online) 1958-5381
    ISSN 0767-0974
    DOI 10.1051/medsci/2019129
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: HIV-1 Env induces pexophagy and an oxidative stress leading to uninfected CD4

    Daussy, Coralie F / Galais, Mathilde / Pradel, Baptiste / Robert-Hebmann, Véronique / Sagnier, Sophie / Pattingre, Sophie / Biard-Piechaczyk, Martine / Espert, Lucile

    Autophagy

    2020  Volume 17, Issue 9, Page(s) 2465–2474

    Abstract: The immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander ... ...

    Abstract The immunodeficiency observed in HIV-1-infected patients is mainly due to uninfected bystander CD4
    MeSH term(s) Autophagy ; CD4-Positive T-Lymphocytes ; Cell Death ; HIV-1 ; Humans ; Macroautophagy ; Oxidative Stress ; T-Lymphocytes
    Language English
    Publishing date 2020-10-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2020.1831814
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: HIV-1 Vpr inhibits autophagy during the early steps of infection of CD4 T cells.

    Alfaisal, Jamal / Machado, Alice / Galais, Mathilde / Robert-Hebmann, Véronique / Arnauné-Pelloquin, Laetitia / Espert, Lucile / Biard-Piechaczyk, Martine

    Biology of the cell

    2019  Volume 111, Issue 12, Page(s) 308–318

    Abstract: Background information: Autophagy is induced during HIV-1 entry into CD4 T cells by the fusion of the membranes triggered by the gp41 envelope glycoprotein. This anti-HIV-1 mechanism is inhibited by the viral infectivity factor (Vif) neosynthesized ... ...

    Abstract Background information: Autophagy is induced during HIV-1 entry into CD4 T cells by the fusion of the membranes triggered by the gp41 envelope glycoprotein. This anti-HIV-1 mechanism is inhibited by the viral infectivity factor (Vif) neosynthesized after HIV-1 integration to allow viral replication. However, autophagy is very rapidly controlled after HIV-1 entry by a still unknown mechanism. As HIV-1 viral protein R (Vpr) is the only auxiliary protein found within the virion in substantial amount, we studied its capability to control the early steps of HIV-1 envelope-mediated autophagy.
    Results: We demonstrated that ectopic Vpr inhibits autophagy in both the Jurkat CD4 T cell line and HEK.293T cells. Interestingly, Vpr coming from the virus also blocks autophagy in CD4 T cells, the main cell target of HIV-1. Furthermore, Vpr decreases the expression level of two essential autophagy proteins (ATG), LC3B and Beclin-1, and an important autophagy-related protein, BNIP3 as well as the level of their mRNA. We also demonstrated in HEK.293T cells that Vpr degrades the FOXO3a transcription factor through the ubiquitin proteasome system.
    Conclusion: Vpr, the only well-expressed HIV-1 auxiliary protein incorporated into viruses, is able to negatively control autophagy induced during HIV-1 entry into CD4 T cells.
    Significance: We provide insights of how HIV-1 controls autophagy very early after its entry into CD4 T cells and discovered a new function of Vpr. These results open the route to a better understanding of the roles of Vpr during HIV-1 infection through FOXO3a degradation and could be important to consider additional therapies that counteract the role of Vpr on autophagy.
    MeSH term(s) Autophagy/immunology ; Beclin-1/immunology ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/immunology ; HEK293 Cells ; HIV Infections/immunology ; HIV-1/immunology ; HIV-1/physiology ; Humans ; Jurkat Cells ; Membrane Proteins/immunology ; Microtubule-Associated Proteins/immunology ; Proto-Oncogene Proteins/immunology ; Tumor Suppressor Proteins/immunology ; Virus Replication ; vpr Gene Products, Human Immunodeficiency Virus/immunology
    Chemical Substances BECN1 protein, human ; BNIP3L protein, human ; Beclin-1 ; MAP1LC3B protein, human ; Membrane Proteins ; Microtubule-Associated Proteins ; Proto-Oncogene Proteins ; Tumor Suppressor Proteins ; vpr Gene Products, Human Immunodeficiency Virus ; vpr protein, Human immunodeficiency virus 1
    Language English
    Publishing date 2019-10-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 245745-3
    ISSN 1768-322X ; 0399-0311 ; 0248-4900
    ISSN (online) 1768-322X
    ISSN 0399-0311 ; 0248-4900
    DOI 10.1111/boc.201900071
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Brief Report: Impaired CD4 T-Cell Response to Autophagy in Treated HIV-1-Infected Individuals.

    Gómez-Mora, Elisabet / Robert-Hebmann, Véronique / García, Elisabet / Massanella, Marta / Clotet, Bonaventura / Cabrera, Cecilia / Blanco, Julià / Biard-Piechaczyk, Martine

    Journal of acquired immune deficiency syndromes (1999)

    2016  Volume 74, Issue 2, Page(s) 201–205

    Abstract: Autophagy restricts infection of CD4 T lymphocytes by HIV-1, but little is known about autophagy in treated HIV-1-infected individuals. We have analyzed the capability of CD4 T cells from aviremic-treated individuals to trigger autophagy and correlated ... ...

    Abstract Autophagy restricts infection of CD4 T lymphocytes by HIV-1, but little is known about autophagy in treated HIV-1-infected individuals. We have analyzed the capability of CD4 T cells from aviremic-treated individuals to trigger autophagy and correlated this response with parameters known to be important for immunological recovery. Autophagy was significantly decreased in CD4 T cells from HIV-1-treated individuals compared with uninfected controls, and this defective autophagic response was more pronounced in individuals with poor CD4 T-cell recovery, suggesting a link between impaired autophagy in CD4 T cells and chronic immunological defects that remain in treated HIV infection.
    MeSH term(s) Adult ; Anti-Retroviral Agents/therapeutic use ; Autophagy ; CD4-Positive T-Lymphocytes/immunology ; Cross-Sectional Studies ; Female ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV Infections/pathology ; HIV Infections/virology ; HIV-1/immunology ; Humans ; Male ; Middle Aged ; Pilot Projects
    Chemical Substances Anti-Retroviral Agents
    Language English
    Publishing date 2016-10-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645053-2
    ISSN 1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
    ISSN (online) 1944-7884 ; 1077-9450
    ISSN 0897-5965 ; 0894-9255 ; 1525-4135
    DOI 10.1097/QAI.0000000000001201
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Apoptosis of uninfected cells induced by HIV envelope glycoproteins

    Biard-Piechaczyk Martine / Devaux Christian / Robert-Hebmann Véronique / Ahr Barbara

    Retrovirology, Vol 1, Iss 1, p

    2004  Volume 12

    Abstract: Abstract Apoptosis, or programmed cell death, is a key event in biologic homeostasis but is also involved in the pathogenesis of many human diseases including human immunodeficiency virus (HIV) infection. Although multiple mechanisms contribute to the ... ...

    Abstract Abstract Apoptosis, or programmed cell death, is a key event in biologic homeostasis but is also involved in the pathogenesis of many human diseases including human immunodeficiency virus (HIV) infection. Although multiple mechanisms contribute to the gradual T cell decline that occurs in HIV-infected patients, programmed cell death of uninfected bystander T lymphocytes, including CD4+ and CD8+ T cells, is an important event leading to immunodeficiency. The HIV envelope glycoproteins (Env) play a crucial role in transducing this apoptotic signal after binding to its receptors, the CD4 molecule and a coreceptor, essentially CCR5 and CXCR4. Depending on Env presentation, the receptor involved and the complexity of target cell contact, apoptosis induction is related to death receptor and/or mitochondria-dependent pathways. This review summarizes current knowledge of Env-mediated cell death leading to T cell depletion and clinical complications and covers the sometimes conflicting studies that address the possible mechanisms of T cell death.
    Keywords Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Immunologic diseases. Allergy ; RC581-607
    Subject code 610 ; 570
    Language English
    Publishing date 2004-06-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Apoptosis of uninfected cells induced by HIV envelope glycoproteins.

    Ahr, Barbara / Robert-Hebmann, Véronique / Devaux, Christian / Biard-Piechaczyk, Martine

    Retrovirology

    2004  Volume 1, Page(s) 12

    Abstract: Apoptosis, or programmed cell death, is a key event in biologic homeostasis but is also involved in the pathogenesis of many human diseases including human immunodeficiency virus (HIV) infection. Although multiple mechanisms contribute to the gradual T ... ...

    Abstract Apoptosis, or programmed cell death, is a key event in biologic homeostasis but is also involved in the pathogenesis of many human diseases including human immunodeficiency virus (HIV) infection. Although multiple mechanisms contribute to the gradual T cell decline that occurs in HIV-infected patients, programmed cell death of uninfected bystander T lymphocytes, including CD4+ and CD8+ T cells, is an important event leading to immunodeficiency. The HIV envelope glycoproteins (Env) play a crucial role in transducing this apoptotic signal after binding to its receptors, the CD4 molecule and a coreceptor, essentially CCR5 and CXCR4. Depending on Env presentation, the receptor involved and the complexity of target cell contact, apoptosis induction is related to death receptor and/or mitochondria-dependent pathways. This review summarizes current knowledge of Env-mediated cell death leading to T cell depletion and clinical complications and covers the sometimes conflicting studies that address the possible mechanisms of T cell death.
    MeSH term(s) Apoptosis/drug effects ; Gene Products, env/pharmacology ; HIV ; HIV Infections/immunology ; HIV Infections/pathology ; Humans ; Lymphocyte Depletion ; T-Lymphocytes/pathology
    Chemical Substances Gene Products, env
    Language English
    Publishing date 2004-06-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 1742-4690
    ISSN (online) 1742-4690
    DOI 10.1186/1742-4690-1-12
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Autophagy restricts HIV-1 infection by selectively degrading Tat in CD4+ T lymphocytes.

    Sagnier, Sophie / Daussy, Coralie F / Borel, Sophie / Robert-Hebmann, Véronique / Faure, Mathias / Blanchet, Fabien P / Beaumelle, Bruno / Biard-Piechaczyk, Martine / Espert, Lucile

    Journal of virology

    2014  Volume 89, Issue 1, Page(s) 615–625

    Abstract: Unlabelled: Autophagy is a ubiquitous mechanism involved in the lysosomal-mediated degradation of cellular components when they are engulfed in vacuoles called autophagosomes. Autophagy is also recognized as an important regulator of the innate and ... ...

    Abstract Unlabelled: Autophagy is a ubiquitous mechanism involved in the lysosomal-mediated degradation of cellular components when they are engulfed in vacuoles called autophagosomes. Autophagy is also recognized as an important regulator of the innate and adaptive immune responses against numerous pathogens, which have, therefore, developed strategies to block or use the autophagy machinery to their own benefit. Upon human immunodeficiency virus type 1 (HIV-1) infection, viral envelope (Env) glycoproteins induce autophagy-dependent apoptosis of uninfected bystander CD4(+) T lymphocytes, a mechanism likely contributing to the loss of CD4(+) T cells. In contrast, in productively infected CD4(+) T cells, HIV-1 is able to block Env-induced autophagy in order to avoid its antiviral effect. To date, nothing is known about how autophagy restricts HIV-1 infection in CD4(+) T lymphocytes. Here, we report that autophagy selectively degrades the HIV-1 transactivator Tat, a protein essential for viral transcription and virion production. We demonstrated that this selective autophagy-mediated degradation of Tat relies on its ubiquitin-independent interaction with the p62/SQSTM1 adaptor. Taken together, our results provide evidence that the anti-HIV effect of autophagy is specifically due to the degradation of the viral transactivator Tat but that this process is rapidly counteracted by the virus to favor its replication and spread.
    Importance: Autophagy is recognized as one of the most ancient and conserved mechanisms of cellular defense against invading pathogens. Cross talk between HIV-1 and autophagy has been demonstrated depending on the virally challenged cell type, and HIV-1 has evolved strategies to block this process to replicate efficiently. However, the mechanisms by which autophagy restricts HIV-1 infection remain to be elucidated. Here, we report that the HIV-1 transactivator Tat, a protein essential for viral replication, is specifically degraded by autophagy in CD4(+) T lymphocytes. Both Tat present in infected cells and incoming Tat secreted from infected cells are targeted for autophagy degradation through a ubiquitin-independent interaction with the autophagy receptor p62/SQSTM1. This study is the first to demonstrate that selective autophagy can be an antiviral process by degrading a viral transactivator. In addition, the results could help in the design of new therapies against HIV-1 by specifically targeting this mechanism.
    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Autophagy ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/virology ; Cells, Cultured ; HIV-1/immunology ; Humans ; Sequestosome-1 Protein ; tat Gene Products, Human Immunodeficiency Virus/metabolism
    Chemical Substances Adaptor Proteins, Signal Transducing ; SQSTM1 protein, human ; Sequestosome-1 Protein ; tat Gene Products, Human Immunodeficiency Virus
    Language English
    Publishing date 2014-10-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.02174-14
    Database MEDical Literature Analysis and Retrieval System OnLINE

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