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  1. Article ; Online: Autophagy-Associated Proteins Control Ebola Virus Internalization Into Host Cells.

    Shtanko, Olena / Reyes, Ann N / Jackson, William T / Davey, Robert A

    The Journal of infectious diseases

    2018  Volume 218, Issue suppl_5, Page(s) S346–S354

    Abstract: Ebola virus (EBOV) enters host cells by macropinocytosis, a poorly understood process. Recent studies have suggested that cell factors involved in autophagy, an evolutionally conserved pathway leading to the lysosomal degradation of protein aggregates ... ...

    Abstract Ebola virus (EBOV) enters host cells by macropinocytosis, a poorly understood process. Recent studies have suggested that cell factors involved in autophagy, an evolutionally conserved pathway leading to the lysosomal degradation of protein aggregates and organelles during cellular stress, also have roles in macropinocytosis. Here, we demonstrate that autophagy-associated proteins are required for trafficking of EBOV into the cell body. Depleting cells of beclin 1, autophagy-related protein 7, or microtubule-associated protein 1A/B light chain 3B (LC3B) abolished EBOV uptake, owing to a block in vesicle formation at the cell surface. Both LC3B-I and LC3B-II interacted with macropinocytic structures. Our work indicates that, although various forms of LC3B possess an inherent ability to associate with forming macropinosomes, LC3B-II is critical for internalization of macropinocytic vesicles and, therefore, EBOV from the cell surface.
    MeSH term(s) Animals ; Autophagy/physiology ; Autophagy-Related Protein 7/metabolism ; Beclin-1/metabolism ; Cell Line ; Cell Line, Tumor ; Chlorocebus aethiops ; Ebolavirus/pathogenicity ; Endocytosis/physiology ; Endosomes/physiology ; HEK293 Cells ; HeLa Cells ; Hemorrhagic Fever, Ebola/metabolism ; Hemorrhagic Fever, Ebola/virology ; Humans ; Lysosomes/metabolism ; Membrane Proteins/metabolism ; Microtubule-Associated Proteins/metabolism ; Vero Cells ; Virus Internalization
    Chemical Substances Beclin-1 ; Membrane Proteins ; Microtubule-Associated Proteins ; Autophagy-Related Protein 7 (EC 6.2.1.45)
    Keywords covid19
    Language English
    Publishing date 2018-10-03
    Publishing country United States
    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.
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiy294
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Retro-2 and its dihydroquinazolinone derivatives inhibit filovirus infection.

    Shtanko, Olena / Sakurai, Yasuteru / Reyes, Ann N / Noël, Romain / Cintrat, Jean-Christophe / Gillet, Daniel / Barbier, Julien / Davey, Robert A

    Antiviral research

    2018  Volume 149, Page(s) 154–163

    Abstract: Members of the family Filoviridae cause severe, often fatal disease in humans, for which there are no approved vaccines and only a few experimental drugs tested in animal models. Retro-2, a small molecule that inhibits retrograde trafficking of bacterial ...

    Abstract Members of the family Filoviridae cause severe, often fatal disease in humans, for which there are no approved vaccines and only a few experimental drugs tested in animal models. Retro-2, a small molecule that inhibits retrograde trafficking of bacterial and plant toxins inside host cells, has been demonstrated to be effective against a range of bacterial and virus pathogens, both in vitro and in animal models. Here, we demonstrated that Retro-2 and its derivatives, Retro-2.1 and compound 25, blocked infection by Ebola virus and Marburg virus in vitro. We show that the derivatives were more potent inhibitors of infection as compared to the parent compound. Pseudotyped virus assays indicated that the compounds affected virus entry into cells while virus particle localization to Niemann-Pick C1-positive compartments showed that they acted at a late step in virus entry. Our work demonstrates a potential for Retro-type drugs to be developed into anti-filoviral therapeutics.
    MeSH term(s) Animals ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Benzamides/chemistry ; Benzamides/pharmacology ; Cell Line ; Cells, Cultured ; Dose-Response Relationship, Drug ; Ebolavirus/drug effects ; Ebolavirus/physiology ; Filoviridae/drug effects ; Filoviridae/physiology ; Humans ; Marburgvirus/drug effects ; Marburgvirus/physiology ; Microbial Sensitivity Tests ; Molecular Structure ; Thiophenes/chemistry ; Thiophenes/pharmacology ; Virus Internalization/drug effects
    Chemical Substances 2-(((5-methyl-2-thienyl)methylene)amino)-N-phenylbenzamide ; Antiviral Agents ; Benzamides ; Thiophenes
    Language English
    Publishing date 2018
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 306628-9
    ISSN 1872-9096 ; 0166-3542
    ISSN (online) 1872-9096
    ISSN 0166-3542
    DOI 10.1016/j.antiviral.2017.11.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Spermine and Spermidine Alter Gene Expression and Antigenic Profile of Borrelia burgdorferi.

    Lin, Ying-Han / Romo, Jesus A / Smith, Trever C / Reyes, Ann N / Karna, S L Rajasekhar / Miller, Christine L / Van Laar, Tricia A / Yendapally, Raghunandan / Chambers, James P / Seshu, J

    Infection and immunity

    2017  Volume 85, Issue 3

    Abstract: ... Borrelia ... ...

    Abstract Borrelia burgdorferi
    MeSH term(s) Antigens, Bacterial/genetics ; Antigens, Bacterial/immunology ; Bacterial Proteins/genetics ; Bacterial Proteins/immunology ; Bacterial Proteins/metabolism ; Biological Transport ; Borrelia burgdorferi/physiology ; Gene Expression Regulation, Bacterial/drug effects ; Humans ; Lyme Disease/immunology ; Lyme Disease/microbiology ; Polyamines/metabolism ; Polyamines/pharmacology ; Spermidine/metabolism ; Spermidine/pharmacology ; Spermine/metabolism ; Spermine/pharmacology ; Transcription, Genetic ; Virulence Factors/genetics
    Chemical Substances Antigens, Bacterial ; Bacterial Proteins ; Polyamines ; Virulence Factors ; Spermine (2FZ7Y3VOQX) ; Spermidine (U87FK77H25)
    Language English
    Publishing date 2017-02-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 218698-6
    ISSN 1098-5522 ; 0019-9567
    ISSN (online) 1098-5522
    ISSN 0019-9567
    DOI 10.1128/IAI.00684-16
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Facile Discovery of a Diverse Panel of Anti-Ebola Virus Antibodies by Immune Repertoire Mining.

    Wang, Bo / Kluwe, Christien A / Lungu, Oana I / DeKosky, Brandon J / Kerr, Scott A / Johnson, Erik L / Jung, Jiwon / Rezigh, Alec B / Carroll, Sean M / Reyes, Ann N / Bentz, Janelle R / Villanueva, Itamar / Altman, Amy L / Davey, Robert A / Ellington, Andrew D / Georgiou, George

    Scientific reports

    2015  Volume 5, Page(s) 13926

    Abstract: The ongoing evolution of Ebolaviruses poses significant challenges to the development of immunodiagnostics for detecting emergent viral variants. There is a critical need for the discovery of monoclonal antibodies with distinct affinities and ... ...

    Abstract The ongoing evolution of Ebolaviruses poses significant challenges to the development of immunodiagnostics for detecting emergent viral variants. There is a critical need for the discovery of monoclonal antibodies with distinct affinities and specificities for different Ebolaviruses. We developed an efficient technology for the rapid discovery of a plethora of antigen-specific monoclonal antibodies from immunized animals by mining the VH:VL paired antibody repertoire encoded by highly expanded B cells in the draining popliteal lymph node (PLN). This approach requires neither screening nor selection for antigen-binding. Specifically we show that mouse immunization with Ebola VLPs gives rise to a highly polarized antibody repertoire in CD138(+) antibody-secreting cells within the PLN. All highly expanded antibody clones (7/7 distinct clones/animal) were expressed recombinantly, and shown to recognize the VLPs used for immunization. Using this approach we obtained diverse panels of antibodies including: (i) antibodies with high affinity towards GP; (ii) antibodies which bound Ebola VLP Kissidougou-C15, the strain circulating in the recent West African outbreak; (iii) non-GP binding antibodies that recognize wild type Sudan or Bundibugyo viruses that have 39% and 37% sequence divergence from Ebola virus, respectively and (iv) antibodies to the Reston virus GP for which no antibodies have been reported.
    MeSH term(s) Animals ; Antibodies, Viral/genetics ; Antibodies, Viral/immunology ; Antibody Formation/genetics ; Antibody Formation/immunology ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Cross Reactions ; Disease Models, Animal ; Ebolavirus/immunology ; Epitopes/genetics ; Epitopes/immunology ; Hemorrhagic Fever, Ebola/genetics ; Hemorrhagic Fever, Ebola/immunology ; Humans ; Immunization ; Immunoglobulin G/genetics ; Immunoglobulin G/immunology ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Heavy Chains/immunology ; Immunoglobulin Light Chains/genetics ; Immunoglobulin Light Chains/immunology ; Immunoglobulin Variable Region/genetics ; Immunoglobulin Variable Region/immunology ; Lymph Nodes/immunology ; Mice ; Phenotype ; Protein Binding/immunology
    Chemical Substances Antibodies, Viral ; Epitopes ; Immunoglobulin G ; Immunoglobulin Heavy Chains ; Immunoglobulin Light Chains ; Immunoglobulin Variable Region
    Language English
    Publishing date 2015-09-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep13926
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Corrigendum: Facile Discovery of a Diverse Panel of Anti-Ebola Virus Antibodies by Immune Repertoire Mining.

    Wang, Bo / Kluwe, Christien A / Lungu, Oana I / DeKosky, Brandon J / Kerr, Scott A / Johnson, Erik L / Tanno, Hidetaka / Lee, Chang-Han / Jung, Jiwon / Rezigh, Alec B / Carroll, Sean M / Reyes, Ann N / Bentz, Janelle R / Villanueva, Itamar / Altman, Amy L / Davey, Robert A / Ellington, Andrew D / Georgiou, George

    Scientific reports

    2016  Volume 6, Page(s) 27229

    Language English
    Publishing date 2016-06-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep27229
    Database MEDical Literature Analysis and Retrieval System OnLINE

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