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Book ; Online: T help in the setting of a persistent viral infection

Greczmiel, Ute

2017

Abstract: Dissertation, ETH Zürich, 2017, No. ... ...

Abstract	Dissertation, ETH Zürich, 2017, No. 24149
Keywords	PATHOGENESE VIRALER INFEKTIONEN (VIROLOGIE) ; PERSISTENZ + LATENZ (VIROLOGIE) ; IMMUNREAKTION + IMMUNANTWORT (IMMUNOLOGIE) ; HELFERZELLEN (IMMUNOLOGIE) ; ANTIKÖRPER + IMMUNOGLOBULINE + GAMMAGLOBULINE (IMMUNOLOGIE)
Language	English
Publisher	Zürich
Publishing country	ch
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Thesis ; Online: T help in the setting of a persistent viral infection

Greczmiel, Ute

2017

Keywords	PATHOGENESE VIRALER INFEKTIONEN (VIROLOGIE) ; PERSISTENZ + LATENZ (VIROLOGIE) ; IMMUNREAKTION + IMMUNANTWORT (IMMUNOLOGIE) ; HELFERZELLEN (IMMUNOLOGIE) ; ANTIKÖRPER + IMMUNOGLOBULINE + GAMMAGLOBULINE (IMMUNOLOGIE) ; PATHOGENESIS OF VIRAL INFECTIONS (VIROLOGY) ; PERSISTENCE + LATENCY (VIROLOGY) ; IMMUNE REACTION + IMMUNE RESPONSE (IMMUNOLOGY) ; HELPER T LYMPHOCYTES (IMMUNOLOGY) ; ANTIBODIES + IMMUNOGLOBULINS + GAMMA GLOBULINS (IMMUNOLOGY) ; info:eu-repo/classification/ddc/610 ; Medical sciences ; medicine
Language	English
Publisher	ETH Zurich
Publishing country	ch
Document type	Thesis ; Online
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Article: The Janus Face of Follicular T Helper Cells in Chronic Viral Infections.

Greczmiel, Ute / Oxenius, Annette

Frontiers in immunology

2018 Volume 9, Page(s) 1162

Abstract: Chronic infections with non-cytopathic viruses constitutively expose virus-specific adaptive immune cells to cognate antigen, requiring their numeric and functional adaptation. Virus-specific CD8 T cells are compromised by various means in their effector ...

Abstract	Chronic infections with non-cytopathic viruses constitutively expose virus-specific adaptive immune cells to cognate antigen, requiring their numeric and functional adaptation. Virus-specific CD8 T cells are compromised by various means in their effector functions, collectively termed T cell exhaustion. Alike CD8 T cells, virus-specific CD4 Th1 cell responses are gradually downregulated but instead, follicular T helper (T
MeSH term(s)	Animals ; Antibodies, Viral/metabolism ; Autoimmunity ; B-Lymphocytes/immunology ; Cell Differentiation ; Chronic Disease ; Cytokines/metabolism ; Germinal Center/immunology ; Humans ; Hypergammaglobulinemia/etiology ; Hypergammaglobulinemia/immunology ; Immune Tolerance ; Immunity, Humoral ; Lymphocyte Activation ; T-Lymphocytes, Helper-Inducer/physiology ; Virus Diseases/complications ; Virus Diseases/immunology
Chemical Substances	Antibodies, Viral ; Cytokines
Language	English
Publishing date	2018-05-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2018.01162
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Article ; Online: Landornamides: Antiviral Ornithine-Containing Ribosomal Peptides Discovered through Genome Mining.

Bösch, Nina M / Borsa, Mariana / Greczmiel, Ute / Morinaka, Brandon I / Gugger, Muriel / Oxenius, Annette / Vagstad, Anna L / Piel, Jörn

Angewandte Chemie (International ed. in English)

2020 Volume 59, Issue 29, Page(s) 11763–11768

Abstract: Proteusins are a family of bacterial ribosomal peptides that largely remain hypothetical genome-predicted metabolites. The only known members are the polytheonamide-type cytotoxins, which have complex structures due to numerous unusual posttranslational ... ...

Abstract	Proteusins are a family of bacterial ribosomal peptides that largely remain hypothetical genome-predicted metabolites. The only known members are the polytheonamide-type cytotoxins, which have complex structures due to numerous unusual posttranslational modifications (PTMs). Cyanobacteria contain large numbers of putative proteusin loci. To investigate their chemical and pharmacological potential beyond polytheonamide-type compounds, we characterized landornamide A, the product of the silent osp gene cluster from Kamptonema sp. PCC 6506. Pathway reconstruction in E. coli revealed a peptide combining lanthionines, d-residues, and, unusually, two ornithines introduced by the arginase-like enzyme OspR. Landornamide A inhibited lymphocytic choriomeningitis virus infection in mouse cells, thus making it one of the few known anti-arenaviral compounds. These data support proteusins as a rich resource of chemical scaffolds, new maturation enzymes, and bioactivities.
MeSH term(s)	Animals ; Antiviral Agents/chemical synthesis ; Antiviral Agents/pharmacology ; Bacterial Proteins/chemical synthesis ; Bacterial Proteins/pharmacology ; Cell Line ; Computational Biology ; Cyanobacteria/chemistry ; Data Mining ; Databases, Genetic ; Escherichia coli/genetics ; Lymphocytic Choriomeningitis/drug therapy ; Lymphocytic choriomeningitis virus ; Mice ; Multigene Family ; Ornithine/chemistry ; Peptides/chemical synthesis ; Peptides/chemistry ; Peptides/pharmacology ; Protein Processing, Post-Translational ; Ribosomal Proteins/chemical synthesis ; Ribosomal Proteins/pharmacology ; Ribosomes/chemistry
Chemical Substances	Antiviral Agents ; Bacterial Proteins ; Peptides ; Ribosomal Proteins ; landornamide a ; Ornithine (E524N2IXA3)
Language	English
Publishing date	2020-05-18
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.201916321
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Article ; Online: Genome-based discovery and total synthesis of janustatins, potent cytotoxins from a plant-associated bacterium.

Ueoka, Reiko / Sondermann, Philipp / Leopold-Messer, Stefan / Liu, Yizhou / Suo, Rei / Bhushan, Agneya / Vadakumchery, Lida / Greczmiel, Ute / Yashiroda, Yoko / Kimura, Hiromi / Nishimura, Shinichi / Hoshikawa, Yojiro / Yoshida, Minoru / Oxenius, Annette / Matsunaga, Shigeki / Williamson, R Thomas / Carreira, Erick M / Piel, Jörn

Nature chemistry

2022 Volume 14, Issue 10, Page(s) 1193–1201

Abstract: Host-associated bacteria are increasingly being recognized as underexplored sources of bioactive natural products with unprecedented chemical scaffolds. A recently identified example is the plant-root-associated marine bacterium Gynuella sunshinyii of ... ...

Abstract	Host-associated bacteria are increasingly being recognized as underexplored sources of bioactive natural products with unprecedented chemical scaffolds. A recently identified example is the plant-root-associated marine bacterium Gynuella sunshinyii of the chemically underexplored order Oceanospirillales. Its genome contains at least 22 biosynthetic gene clusters, suggesting a rich and mostly uncharacterized specialized metabolism. Here, in silico chemical prediction of a non-canonical polyketide synthase cluster has led to the discovery of janustatins, structurally unprecedented polyketide alkaloids with potent cytotoxicity that are produced in minute quantities. A combination of MS and two-dimensional NMR experiments, density functional theory calculations of
MeSH term(s)	Bacteria/metabolism ; Biological Products/chemistry ; Cytotoxins/metabolism ; Cytotoxins/pharmacology ; Polyketide Synthases/metabolism ; Polyketides/metabolism
Chemical Substances	Biological Products ; Cytotoxins ; Polyketides ; Polyketide Synthases (79956-01-7)
Language	English
Publishing date	2022-09-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2464596-5
ISSN	1755-4349 ; 1755-4330
ISSN (online)	1755-4349
ISSN	1755-4330
DOI	10.1038/s41557-022-01020-0
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Article ; Online: LCMV-specific CD4 T cell dependent polyclonal B-cell activation upon persistent viral infection is short lived and extrafollicular.

Greczmiel, Ute / Kräutler, Nike J / Borsa, Mariana / Pedrioli, Alessandro / Bartsch, Ilka / Richter, Kirsten / Agnellini, Paola / Bedenikovic, Gregor / Oxenius, Annette

European journal of immunology

2019 Volume 50, Issue 3, Page(s) 396–403

Abstract: Persistent virus infections with non- or poorly cytopathic viruses are commonly associated with B cell dysregulations. These include the induction of hypergammaglobulinemia and the emergence of virus-unspecific antibodies. These seemingly unspecific ... ...

Abstract	Persistent virus infections with non- or poorly cytopathic viruses are commonly associated with B cell dysregulations. These include the induction of hypergammaglobulinemia and the emergence of virus-unspecific antibodies. These seemingly unspecific antibody responses interfere with the virus-specific humoral immunity and contribute to delayed virus control. Whether these virus-unspecific antibodies are induced in the B cell follicle or at extrafollicular sites and whether one specific CD4 T cell subset is involved in the polyclonal B cell activation is unclear. Here we studied virus-unrelated IgG antibody responses against self or foreign antigens in the context of persistent lymphocytic choriomeningitis virus (LCMV) infection. We found that the LCMV-unspecific antibody response is short-lived and induced predominantly at extrafollicular sites and depends on the presence of LCMV-specific CD4 T cells. Our data support a scenario in which activated, virus-specific CD4 T cells provide help to non-specific B cells at extrafollicular sites, supporting the production of virus unspecific IgG antibodies during persistent viral infection.
MeSH term(s)	Animals ; Antibodies, Viral/immunology ; B-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/immunology ; Immunoglobulin G/immunology ; Lymphocyte Activation/immunology ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic choriomeningitis virus/immunology ; Mice, Inbred C57BL
Chemical Substances	Antibodies, Viral ; Immunoglobulin G
Language	English
Publishing date	2019-11-27
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.201948286
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Zs.A 489: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Sustained T follicular helper cell response is essential for control of chronic viral infection.

Greczmiel, Ute / Kräutler, Nike Julia / Pedrioli, Alessandro / Bartsch, Ilka / Agnellini, Paola / Bedenikovic, Gregor / Harker, James / Richter, Kirsten / Oxenius, Annette

Science immunology

2017 Volume 2, Issue 18

Abstract: During chronic viral infections, both CD8 and CD4 T cell responses are functionally compromised. Alongside exhaustion of CD8 T cells during chronic viral infections, it has also been documented that the CD4 T cells have an increased propensity to ... ...

Abstract	During chronic viral infections, both CD8 and CD4 T cell responses are functionally compromised. Alongside exhaustion of CD8 T cells during chronic viral infections, it has also been documented that the CD4 T cells have an increased propensity to differentiate toward CXCR5
MeSH term(s)	Animals ; Chronic Disease ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic choriomeningitis virus/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; T-Lymphocytes, Helper-Inducer/immunology
Language	English
Publishing date	2017-11-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.aam8686
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Article ; Online: Quantitative and Qualitative Analysis of Humoral Immunity Reveals Continued and Personalized Evolution in Chronic Viral Infection.

Kräutler, Nike Julia / Yermanos, Alexander / Pedrioli, Alessandro / Welten, Suzanne P M / Lorgé, Dominique / Greczmiel, Ute / Bartsch, Ilka / Scheuermann, Jörg / Kiefer, Jonathan D / Eyer, Klaus / Menzel, Ulrike / Greiff, Victor / Neri, Dario / Stadler, Tanja / Reddy, Sai T / Oxenius, Annette

Cell reports

2020 Volume 30, Issue 4, Page(s) 997–1012.e6

Abstract: Control of established chronic lymphocytic choriomeningitis virus (LCMV) infection requires the production of neutralizing antibodies, but it remains unknown how the ensemble of antibodies evolves during ongoing infection. Here, we analyze the evolution ... ...

Abstract	Control of established chronic lymphocytic choriomeningitis virus (LCMV) infection requires the production of neutralizing antibodies, but it remains unknown how the ensemble of antibodies evolves during ongoing infection. Here, we analyze the evolution of antibody responses during acute or chronic LCMV infection, combining quantitative functional assays and time-resolved antibody repertoire sequencing. We establish that antibody responses initially converge in both infection types on a functional and repertoire level, but diverge later during chronic infection, showing increased clonal diversity, the appearance of mouse-specific persistent clones, and distinct phylogenetic signatures. Chronic infection is characterized by a longer-lasting germinal center reaction and a continuous differentiation of plasma cells, resulting in the emergence of higher-affinity plasma cells exhibiting increased antibody secretion rates. Taken together, our findings reveal the emergence of a personalized antibody response in chronic infection and support the concept that maintaining B cell diversity throughout chronic LCMV infection correlates with the development of infection-resolving antibodies.
MeSH term(s)	Acute Disease ; Animals ; Antibodies, Viral/immunology ; Antibody Diversity/genetics ; Antibody Formation/genetics ; B-Lymphocytes/immunology ; Cell Differentiation/genetics ; Cell Differentiation/immunology ; Cell Line ; Chronic Disease ; Clonal Evolution/genetics ; Clonal Evolution/immunology ; Germinal Center/metabolism ; Immunity, Humoral/genetics ; Immunoglobulin G/immunology ; Lymphocytic Choriomeningitis/immunology ; Lymphocytic Choriomeningitis/virology ; Lymphocytic choriomeningitis virus/immunology ; Lymphocytic choriomeningitis virus/pathogenicity ; Mice ; Mice, Inbred C57BL ; Phylogeny ; Plasma Cells/immunology ; Plasma Cells/metabolism ; Somatic Hypermutation, Immunoglobulin
Chemical Substances	Antibodies, Viral ; Immunoglobulin G
Language	English
Publishing date	2020-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2019.12.088
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Article ; Online: Inhibition of Canonical NF-κB Signaling by a Small Molecule Targeting NEMO-Ubiquitin Interaction.

Vincendeau, Michelle / Hadian, Kamyar / Messias, Ana C / Brenke, Jara K / Halander, Jenny / Griesbach, Richard / Greczmiel, Ute / Bertossi, Arianna / Stehle, Ralf / Nagel, Daniel / Demski, Katrin / Velvarska, Hana / Niessing, Dierk / Geerlof, Arie / Sattler, Michael / Krappmann, Daniel

Scientific reports

2016 Volume 6, Page(s) 18934

Abstract: The IκB kinase (IKK) complex acts as the gatekeeper of canonical NF-κB signaling, thereby regulating immunity, inflammation and cancer. It consists of the catalytic subunits IKKα and IKKβ and the regulatory subunit NEMO/IKKγ. Here, we show that the ... ...

Abstract	The IκB kinase (IKK) complex acts as the gatekeeper of canonical NF-κB signaling, thereby regulating immunity, inflammation and cancer. It consists of the catalytic subunits IKKα and IKKβ and the regulatory subunit NEMO/IKKγ. Here, we show that the ubiquitin binding domain (UBAN) in NEMO is essential for IKK/NF-κB activation in response to TNFα, but not IL-1β stimulation. By screening a natural compound library we identified an anthraquinone derivative that acts as an inhibitor of NEMO-ubiquitin binding (iNUB). Using biochemical and NMR experiments we demonstrate that iNUB binds to NEMOUBAN and competes for interaction with methionine-1-linked linear ubiquitin chains. iNUB inhibited NF-κB activation upon UBAN-dependent TNFα and TCR/CD28, but not UBAN-independent IL-1β stimulation. Moreover, iNUB was selectively killing lymphoma cells that are addicted to chronic B-cell receptor triggered IKK/NF-κB activation. Thus, iNUB disrupts the NEMO-ubiquitin protein-protein interaction interface and thereby inhibits physiological and pathological NF-κB signaling.
MeSH term(s)	Animals ; Anthraquinones/pharmacology ; Drug Evaluation, Preclinical ; HeLa Cells ; Humans ; Interleukin-1beta/physiology ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice ; NF-kappa B/metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; Signal Transduction/drug effects ; Tumor Necrosis Factor-alpha/physiology ; Ubiquitin/metabolism ; Ubiquitination
Chemical Substances	Anthraquinones ; Interleukin-1beta ; Intracellular Signaling Peptides and Proteins ; NEMO protein, mouse ; NF-kappa B ; TNF protein, human ; Tumor Necrosis Factor-alpha ; Ubiquitin
Language	English
Publishing date	2016-01-07
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/srep18934
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Article ; Online: Alternative splicing of MALT1 controls signalling and activation of CD4(+) T cells.

Meininger, Isabel / Griesbach, Richard A / Hu, Desheng / Gehring, Torben / Seeholzer, Thomas / Bertossi, Arianna / Kranich, Jan / Oeckinghaus, Andrea / Eitelhuber, Andrea C / Greczmiel, Ute / Gewies, Andreas / Schmidt-Supprian, Marc / Ruland, Jürgen / Brocker, Thomas / Heissmeyer, Vigo / Heyd, Florian / Krappmann, Daniel

Nature communications

2016 Volume 7, Page(s) 11292

Abstract: MALT1 channels proximal T-cell receptor (TCR) signalling to downstream signalling pathways. With MALT1A and MALT1B two conserved splice variants exist and we demonstrate here that MALT1 alternative splicing supports optimal T-cell activation. Inclusion ... ...

Abstract	MALT1 channels proximal T-cell receptor (TCR) signalling to downstream signalling pathways. With MALT1A and MALT1B two conserved splice variants exist and we demonstrate here that MALT1 alternative splicing supports optimal T-cell activation. Inclusion of exon7 in MALT1A facilitates the recruitment of TRAF6, which augments MALT1 scaffolding function, but not protease activity. Naive CD4(+) T cells express almost exclusively MALT1B and MALT1A expression is induced by TCR stimulation. We identify hnRNP U as a suppressor of exon7 inclusion. Whereas selective depletion of MALT1A impairs T-cell signalling and activation, downregulation of hnRNP U enhances MALT1A expression and T-cell activation. Thus, TCR-induced alternative splicing augments MALT1 scaffolding to enhance downstream signalling and to promote optimal T-cell activation.
MeSH term(s)	Alternative Splicing/genetics ; Animals ; CD4-Positive T-Lymphocytes/immunology ; Caspases/genetics ; Caspases/metabolism ; Down-Regulation ; Enzyme Activation ; Exons/genetics ; HEK293 Cells ; Heterogeneous-Nuclear Ribonucleoprotein U/metabolism ; Humans ; Interleukin-2/biosynthesis ; JNK Mitogen-Activated Protein Kinases/metabolism ; Jurkat Cells ; Lymphocyte Activation/immunology ; Mice, Inbred C57BL ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein ; NF-kappa B/metabolism ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Receptors, Antigen, T-Cell/metabolism ; Signal Transduction ; TNF Receptor-Associated Factor 6/metabolism ; Th17 Cells/immunology ; Up-Regulation
Chemical Substances	Heterogeneous-Nuclear Ribonucleoprotein U ; Interleukin-2 ; NF-kappa B ; Neoplasm Proteins ; Receptors, Antigen, T-Cell ; TNF Receptor-Associated Factor 6 ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Caspases (EC 3.4.22.-) ; MALT1 protein, human (EC 3.4.22.-) ; Malt1 protein, mouse (EC 3.4.22.-) ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein (EC 3.4.22.-)
Language	English
Publishing date	2016-04-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2041-1723
ISSN (online)	2041-1723
DOI	10.1038/ncomms11292
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