@article{HennigMichalskiRutkowskietal.2018,
  author    = {Hennig, Thomas and Michalski, Marco and Rutkowski, Andrzej J. and Djakovic, Lara and Whisnant, Adam W. and Friedl, Marie-Sophie and Jha, Bhaskar Anand and Baptista, Marisa A. P. and L'Hernault, Anne and Erhard, Florian and D{\"o}lken, Lars and Friedel, Caroline C.},
  title     = {HSV-1-induced disruption of transcription termination resembles a cellular stress response but selectively increases chromatin accessibility downstream of genes},
  series = {PLoS Pathogens},
  volume    = {14},
  journal   = {PLoS Pathogens},
  number    = {3},
  doi       = {10.1371/journal.ppat.1006954},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176350},
  pages     = {e1006954},
  year      = {2018},
  abstract  = {Lytic herpes simplex virus 1 (HSV-1) infection triggers disruption of transcription termination (DoTT) of most cellular genes, resulting in extensive intergenic transcription. Similarly, cellular stress responses lead to gene-specific transcription downstream of genes (DoG). In this study, we performed a detailed comparison of DoTT/DoG transcription between HSV-1 infection, salt and heat stress in primary human fibroblasts using 4sU-seq and ATAC-seq. Although DoTT at late times of HSV-1 infection was substantially more prominent than DoG transcription in salt and heat stress, poly(A) read-through due to DoTT/DoG transcription and affected genes were significantly correlated between all three conditions, in particular at earlier times of infection. We speculate that HSV-1 either directly usurps a cellular stress response or disrupts the transcription termination machinery in other ways but with similar consequences. In contrast to previous reports, we found that inhibition of Ca\(^{2+}\) signaling by BAPTA-AM did not specifically inhibit DoG transcription but globally impaired transcription. Most importantly, HSV-1-induced DoTT, but not stress-induced DoG transcription, was accompanied by a strong increase in open chromatin downstream of the affected poly(A) sites. In its extent and kinetics, downstream open chromatin essentially matched the poly(A) read-through transcription. We show that this does not cause but rather requires DoTT as well as high levels of transcription into the genomic regions downstream of genes. This raises intriguing new questions regarding the role of histone repositioning in the wake of RNA Polymerase II passage downstream of impaired poly(A) site recognition.},
  language  = {en}
}
@article{NonoPletinckxLutzetal.2012,
  author    = {Nono, Justin Komguep and Pletinckx, Katrien and Lutz, Manfred B. and Brehm, Klaus},
  title     = {Excretory/Secretory-Products of Echinococcus multilocularis Larvae Induce Apoptosis and Tolerogenic Properties in Dendritic Cells In Vitro},
  series = {PLoS Neglected Tropical Diseases},
  volume    = {6},
  journal   = {PLoS Neglected Tropical Diseases},
  number    = {2},
  doi       = {10.1371/journal.pntd.0001516},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134280},
  pages     = {e1516},
  year      = {2012},
  abstract  = {Background: Alveolar echinococcosis, caused by Echinococcus multilocularis larvae, is a chronic disease associated with considerable modulation of the host immune response. Dendritic cells (DC) are key effectors in shaping the immune response and among the first cells encountered by the parasite during an infection. Although it is assumed that E. multilocularis, by excretory/secretory (E/S)-products, specifically affects DC to deviate immune responses, little information is available on the molecular nature of respective E/S-products and their mode of action. Methodology/Principal Findings: We established cultivation systems for exposing DC to live material from early (oncosphere), chronic (metacestode) and late (protoscolex) infectious stages. When co-incubated with Echinococcus primary cells, representing the invading oncosphere, or metacestode vesicles, a significant proportion of DC underwent apoptosis and the surviving DC failed to mature. In contrast, DC exposed to protoscoleces upregulated maturation markers and did not undergo apoptosis. After pre-incubation with primary cells and metacestode vesicles, DC showed a strongly impaired ability to be activated by the TLR ligand LPS, which was not observed in DC pre-treated with protoscolex E/S-products. While none of the larvae induced the secretion of pro-inflammatory IL-12p70, the production of immunosuppressive IL-10 was elevated in response to primary cell E/S-products. Finally, upon incubation with DC and naive T-cells, E/S-products from metacestode vesicles led to a significant expansion of Foxp3+ T cells in vitro. Conclusions: This is the first report on the induction of apoptosis in DC by cestode E/S-products. Our data indicate that the early infective stage of E. multilocularis is a strong inducer of tolerance in DC, which is most probably important for generating an immunosuppressive environment at an infection phase in which the parasite is highly vulnerable to host attacks. The induction of CD4+CD25+Foxp3+ T cells through metacestode E/S-products suggests that these cells fulfill an important role for parasite persistence during chronic echinococcosis.},
  language  = {en}
}
@article{RutkowskiErhardL'Hernaultetal.2015,
  author    = {Rutkowski, Andrzej J. and Erhard, Florian and L'Hernault, Anne and Bonfert, Thomas and Schilhabel, Markus and Crump, Colin and Rosenstiel, Philip and Efstathiou, Stacey and Zimmer, Ralf and Friedel, Caroline C. and D{\"o}lken, Lars},
  title     = {Widespread disruption of host transcription termination in HSV-1 infection},
  series = {Nature Communications},
  volume    = {6},
  journal   = {Nature Communications},
  number    = {7126},
  doi       = {10.1038/ncomms8126},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148643},
  year      = {2015},
  abstract  = {Herpes simplex virus 1 (HSV-1) is an important human pathogen and a paradigm for virus-induced host shut-off. Here we show that global changes in transcription and RNA processing and their impact on translation can be analysed in a single experimental setting by applying 4sU-tagging of newly transcribed RNA and ribosome profiling to lytic HSV-1 infection. Unexpectedly, we find that HSV-1 triggers the disruption of transcription termination of cellular, but not viral, genes. This results in extensive transcription for tens of thousands of nucleotides beyond poly(A) sites and into downstream genes, leading to novel intergenic splicing between exons of neighbouring cellular genes. As a consequence, hundreds of cellular genes seem to be transcriptionally induced but are not translated. In contrast to previous reports, we show that HSV-1 does not inhibit co-transcriptional splicing. Our approach thus substantially advances our understanding of HSV-1 biology and establishes HSV-1 as a model system for studying transcription termination.},
  language  = {en}
}