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  1. Article ; Online: Replication competent HIV-guided CRISPR screen identifies antiviral factors including targets of the accessory protein Nef.

    Prelli Bozzo, Caterina / Laliberté, Alexandre / De Luna, Aurora / Pastorio, Chiara / Regensburger, Kerstin / Krebs, Stefan / Graf, Alexander / Blum, Helmut / Volcic, Meta / Sparrer, Konstantin M J / Kirchhoff, Frank

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 3813

    Abstract: Innate antiviral factors are essential for effective defense against viral pathogens. However, the identity of major restriction mechanisms remains elusive. Current approaches to discover antiviral factors usually focus on the initial steps of viral ... ...

    Abstract Innate antiviral factors are essential for effective defense against viral pathogens. However, the identity of major restriction mechanisms remains elusive. Current approaches to discover antiviral factors usually focus on the initial steps of viral replication and are limited to a single round of infection. Here, we engineered libraries of >1500 replication-competent HIV-1 constructs each expressing a single gRNAs to target >500 cellular genes for virus-driven discovery of antiviral factors. Passaging in CD4
    MeSH term(s) Humans ; HIV-1/genetics ; HIV-1/physiology ; Virus Replication/genetics ; nef Gene Products, Human Immunodeficiency Virus/genetics ; nef Gene Products, Human Immunodeficiency Virus/metabolism ; CD4-Positive T-Lymphocytes/virology ; CD4-Positive T-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/immunology ; HEK293 Cells ; CRISPR-Cas Systems ; HIV Infections/virology ; HIV Infections/genetics ; HIV Infections/immunology ; RNA, Guide, CRISPR-Cas Systems/genetics ; RNA, Guide, CRISPR-Cas Systems/metabolism ; Phosphoproteins/metabolism ; Phosphoproteins/genetics ; rhoA GTP-Binding Protein/metabolism ; rhoA GTP-Binding Protein/genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Virus Internalization
    Chemical Substances nef Gene Products, Human Immunodeficiency Virus ; RNA, Guide, CRISPR-Cas Systems ; Phosphoproteins ; rhoA GTP-Binding Protein (EC 3.6.5.2) ; nef protein, Human immunodeficiency virus 1
    Language English
    Publishing date 2024-05-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-48228-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Luciferase reporter assays to monitor interferon signaling modulation by SARS-CoV-2 proteins.

    Hirschenberger, Maximilian / Hayn, Manuel / Laliberté, Alexandre / Koepke, Lennart / Kirchhoff, Frank / Sparrer, Konstantin Maria Johannes

    STAR protocols

    2021  Volume 2, Issue 4, Page(s) 100781

    Abstract: We present a protocol for analyzing the impact of SARS-CoV-2 proteins in interferon signaling using luciferase reporter assays. Here, the induction of defined promoters can be quantitatively assessed with high sensitivity and broad linear range. The ... ...

    Abstract We present a protocol for analyzing the impact of SARS-CoV-2 proteins in interferon signaling using luciferase reporter assays. Here, the induction of defined promoters can be quantitatively assessed with high sensitivity and broad linear range. The results are similar to those obtained using qPCR to measure endogenous mRNA induction. The assay requires stringent normalization and confirmation of the results in more physiological settings. The protocol is adaptable for other viruses and other innate immune stimuli. For complete details on the use and execution of this protocol, please refer to Hayn et al. (2021).
    MeSH term(s) Antiviral Agents/pharmacology ; COVID-19/drug therapy ; COVID-19/metabolism ; COVID-19/pathology ; COVID-19/virology ; Gene Expression Regulation, Viral/drug effects ; Humans ; Interferons/pharmacology ; Luciferases/genetics ; Luciferases/metabolism ; Promoter Regions, Genetic ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; SARS-CoV-2/drug effects ; SARS-CoV-2/metabolism ; Viral Proteins/genetics ; Viral Proteins/metabolism
    Chemical Substances Antiviral Agents ; RNA, Messenger ; Viral Proteins ; Interferons (9008-11-1) ; Luciferases (EC 1.13.12.-)
    Language English
    Publishing date 2021-08-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2021.100781
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Activation of the ILT7 receptor and plasmacytoid dendritic cell responses are governed by structurally-distinct BST2 determinants.

    Bego, Mariana G / Miguet, Nolwenn / Laliberté, Alexandre / Aschman, Nicolas / Gerard, Francine / Merakos, Angelique A / Weissenhorn, Winfried / Cohen, Éric A

    The Journal of biological chemistry

    2019  Volume 294, Issue 27, Page(s) 10503–10518

    Abstract: Type I interferons (IFN-I) are key innate immune effectors predominantly produced by activated plasmacytoid dendritic cells (pDCs). By modulating immune responses at their foundation, IFNs can widely reshape immunity to control infectious diseases and ... ...

    Abstract Type I interferons (IFN-I) are key innate immune effectors predominantly produced by activated plasmacytoid dendritic cells (pDCs). By modulating immune responses at their foundation, IFNs can widely reshape immunity to control infectious diseases and malignancies. Nevertheless, their biological activities can also be detrimental to surrounding healthy cells, as prolonged IFN-I signaling is associated with excessive inflammation and immune dysfunction. The interaction of the human pDC receptor immunoglobulin-like transcript 7 (ILT7) with its IFN-I-regulated ligand, bone marrow stromal cell antigen 2 (BST2) plays a key role in controlling the IFN-I amounts produced by pDCs in response to Toll-like receptor (TLR) activation. However, the structural determinants and molecular features of BST2 that govern ILT7 engagement and activation are largely undefined. Using two functional assays to measure BST2-stimulated ILT7 activation as well as biophysical studies, here we identified two structurally-distinct regions of the BST2 ectodomain that play divergent roles during ILT7 activation. We found that although the coiled-coil region contains a newly defined ILT7-binding surface, the N-terminal region appears to suppress ILT7 activation. We further show that a stable BST2 homodimer binds to ILT7, but post-binding events associated with the unique BST2 coiled-coil plasticity are required to trigger receptor signaling. Hence, BST2 with an unstable or a rigid coiled-coil fails to activate ILT7, whereas substitutions in its N-terminal region enhance activation. Importantly, the biological relevance of these newly defined domains of BST2 is underscored by the identification of substitutions having opposing potentials to activate ILT7 in pathological malignant conditions.
    MeSH term(s) Amino Acid Sequence ; Bone Marrow Stromal Antigen 2/chemistry ; Bone Marrow Stromal Antigen 2/genetics ; Bone Marrow Stromal Antigen 2/metabolism ; Cell Line ; Dimerization ; Humans ; Mutagenesis ; Protein Binding ; Protein Conformation, alpha-Helical ; Protein Domains ; Receptors, Immunologic/metabolism ; Sequence Alignment
    Chemical Substances Bone Marrow Stromal Antigen 2 ; LILRA4 protein, human ; Receptors, Immunologic
    Language English
    Publishing date 2019-05-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.RA119.008481
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.108: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Vpr attenuates antiviral immune responses and is critical for full pathogenicity of SIV

    Laliberté, Alexandre / Prelli Bozzo, Caterina / Stahl-Hennig, Christiane / Hunszinger, Victoria / Joas, Simone / Sauermann, Ulrike / Roshani, Berit / Klippert, Antonina / Daskalaki, Maria / Mätz-Rensing, Kerstin / Stolte-Leeb, Nicole / Tharp, Gregory K / Fuchs, Dietmar / Gupta, Prachi Mehrotra / Silvestri, Guido / Nelson, Sydney A / Parodi, Laura / Giavedoni, Luis / Bosinger, Steven E /
    Sparrer, Konstantin M J / Kirchhoff, Frank

    iScience

    2023  Volume 26, Issue 12, Page(s) 108351

    Abstract: The accessory viral protein R (Vpr) is encoded by all primate lentiviruses. Vpr counteracts DNA repair pathways, modulates viral immune sensing, and induces cell-cycle arrest in cell culture. However, its ... ...

    Abstract The accessory viral protein R (Vpr) is encoded by all primate lentiviruses. Vpr counteracts DNA repair pathways, modulates viral immune sensing, and induces cell-cycle arrest in cell culture. However, its impact
    Language English
    Publishing date 2023-10-26
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.108351
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo.

    Geretz, Aviva / Ehrenberg, Philip K / Clifford, Robert J / Laliberté, Alexandre / Prelli Bozzo, Caterina / Eiser, Daina / Kundu, Gautam / Yum, Lauren K / Apps, Richard / Creegan, Matthew / Gunady, Mohamed / Shangguan, Shida / Sanders-Buell, Eric / Sacdalan, Carlo / Phanuphak, Nittaya / Tovanabutra, Sodsai / Russell, Ronnie M / Bibollet-Ruche, Frederic / Robb, Merlin L /
    Michael, Nelson L / Ake, Julie A / Vasan, Sandhya / Hsu, Denise C / Hahn, Beatrice H / Kirchhoff, Frank / Thomas, Rasmi

    Science translational medicine

    2023  Volume 15, Issue 707, Page(s) eadg0873

    Abstract: Host restriction factors play key roles in innate antiviral defense, but it remains poorly understood which of them restricts HIV-1 in vivo. Here, we used single-cell transcriptomic analysis to identify host factors associated with HIV-1 control during ... ...

    Abstract Host restriction factors play key roles in innate antiviral defense, but it remains poorly understood which of them restricts HIV-1 in vivo. Here, we used single-cell transcriptomic analysis to identify host factors associated with HIV-1 control during acute infection by correlating host gene expression with viral RNA abundance within individual cells. Wide sequencing of cells from one participant with the highest plasma viral load revealed that intracellular viral RNA transcription correlates inversely with expression of the gene
    MeSH term(s) Humans ; HIV-1/genetics ; Transcriptome/genetics ; HIV Infections/genetics ; RNA, Viral
    Chemical Substances prothymosin alpha ; RNA, Viral
    Language English
    Publishing date 2023-08-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.adg0873
    Database MEDical Literature Analysis and Retrieval System OnLINE

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