This is the institutional Repository of the Helmholtz Centre for Infection Research in Braunschweig/Germany (HZI), the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken/Germany, the TWINCORE Zentrum für Exprerimentelle und Klinische Infektionsforschung, Hannover/Germany,Helmholtz-Institut für RNA-basierte Infektionsforschung (HIRI), BRICS, CSSB and the Study Centre Hannover, Hannover/Germany.

 

  • Chronic hepatitis C virus infection irreversibly impacts human natural killer cell repertoire diversity.

    Strunz, Benedikt; Hengst, Julia; Deterding, Katja; Manns, Michael P; Cornberg, Markus; Ljunggren, Hans-Gustaf; Wedemeyer, Heiner; Björkström, Niklas K; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-06-11)
    Diversity is a central requirement for the immune system's capacity to adequately clear a variety of different infections. As such, natural killer (NK) cells represent a highly diverse population of innate lymphocytes important in the early response against viruses. Yet, the extent to which a chronic pathogen affects NK cell diversity is largely unknown. Here we study NK cell functional diversification in chronic hepatitis C virus (HCV) infection. High-dimensional flow cytometer assays combined with stochastic neighbor embedding analysis reveal that chronic HCV infection induces functional imprinting on human NK cells that is largely irreversible and persists long after successful interventional clearance of the virus. Furthermore, HCV infection increases inter-individual, but decreases intra-individual, NK cell diversity. Taken together, our results provide insights into how the history of infections affects human NK cell diversity.
  • AMBER: Assessment of Metagenome BinnERs.

    Meyer, Fernando; Hofmann, Peter; Belmann, Peter; Garrido-Oter, Ruben; Fritz, Adrian; Sczyrba, Alexander; McHardy, Alice C; BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany. (2018-06-08)
    Reconstructing the genomes of microbial community members is key to the interpretation of shotgun metagenome samples. Genome binning programs deconvolute reads or assembled contigs of such samples into individual bins, but assessing their quality is difficult due to the lack of evaluation software and standardized metrics. We present AMBER, an evaluation package for the comparative assessment of genome reconstructions from metagenome benchmark data sets. It calculates the performance metrics and comparative visualizations used in the first benchmarking challenge of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). As an application, we show the outputs of AMBER for eleven different binning programs on two CAMI benchmark data sets. AMBER is implemented in Python and available under the Apache 2.0 license on GitHub (https://github.com/CAMI-challenge/AMBER).
  • A guiding map for inflammation.

    Netea, Mihai G; Balkwill, Frances; Chonchol, Michel; Cominelli, Fabio; Donath, Marc Y; Giamarellos-Bourboulis, Evangelos J; Golenbock, Douglas; Gresnigt, Mark S; Heneka, Michael T; Hoffman, Hal M; Hotchkiss, Richard; Joosten, Leo A B; Kastner, Daniel L; Korte, Martin; Latz, Eicke; Libby, Peter; Mandrup-Poulsen, Thomas; Mantovani, Alberto; Mills, Kingston H G; Nowak, Kristen L; O'Neill, Luke A; Pickkers, Peter; van der Poll, Tom; Ridker, Paul M; Schalkwijk, Joost; Schwartz, David A; Siegmund, Britta; Steer, Clifford J; Tilg, Herbert; van der Meer, Jos W M; van de Veerdonk, Frank L; Dinarello, Charles A; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2017-07-19)
    Biologists, physicians and immunologists have contributed to the understanding of the cellular participants and biological pathways involved in inflammation. Here, we provide a general guide to the cellular and humoral contributors to inflammation as well as to the pathways that characterize inflammation in specific organs and tissues.
  • The chromatin remodeling factor SPOC1 acts as a cellular restriction factor against human cytomegalovirus by repressing the major immediate-early promoter.

    Reichel, Anna; Stilp, Anne-Charlotte; Scherer, Myriam; Reuter, Nina; Lukassen, Sören; Kasmapour, Bahram; Schreiner, Sabrina; Cicin-Sain, Luka; Winterpacht, Andreas; Stamminger, Thomas; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-05-09)
    The cellular protein SPOC1 (survival time-associated PHD finger protein in ovarian cancer 1) acts as a regulator of chromatin structure and DNA damage response. It binds H3K4me2/3 containing chromatin and promotes DNA condensation by recruiting corepressors such as KAP-1 and H3K9 methyltransferases. Previous studies identified SPOC1 as a restriction factor against human adenovirus (HAdV) infection that is antagonized by E1B-55K/E4orf6-dependent proteasomal degradation. Here, we demonstrate that, in contrast to HAdV-infected cells, SPOC1 is transiently upregulated during the early phase of HCMV replication. We show that expression of the immediate-early protein 1 (IE1) is sufficient and necessary to induce SPOC1. Additionally, we discovered that during later stages of infection SPOC1 is downregulated in a GSK-3β-dependent manner. We provide evidence that SPOC1 overexpression severely impairs HCMV replication by repressing the initiation of viral immediate early (IE) gene expression. Consistently, we observed that SPOC1-depleted primary human fibroblasts displayed augmented initiation of viral IE gene expression. This occurs in a MOI-dependent manner, a defining hallmark of intrinsic immunity. Interestingly, repression requires the presence of high SPOC1 levels at the start of infection while a later upregulation had no negative impact suggesting distinct temporal roles of SPOC1 during the HCMV replicative cycle. Mechanistically, we observed a highly specific association of SPOC1 with the major immediate-early promoter (MIEP) strongly suggesting that SPOC1 inhibits HCMV replication by MIEP binding and subsequent recruitment of heterochromatin building factors. Thus, our data add SPOC1 as a novel factor to the endowment of a host cell to restrict cytomegalovirus infections.
  • New nematicidal and antimicrobial secondary metabolites from a new species in the new genus, .

    Rupcic, Zeljka; Chepkirui, Clara; Hernández-Restrepo, Margarita; Crous, Pedro W; Luangsa-Ard, Janet Jennifer; Stadler, Marc; Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2018-01-01)
    During the course of a study on the functional biodiversity of the mycobiota inhabiting rainforests in Thailand, a fungal strain was isolated from a plant sample and shown to represent an undescribed species, as inferred from a combination of morphological and molecular phylogenetic methods. Molecular phylogenetic analyses, based on four DNA loci, revealed a phylogenetic tree with the newly generated sequences clustering in a separate branch, together with members of the Sulcatisporaceae (Pleosporales, Ascomycota). The Thai specimen morphologically resembled

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