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Dr. Nicole Fischer
University Medical Center Hamburg-Eppendorf, Institute for Medical Microbiology, Virology and Hygiene, Hamburg, Germany

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0 herpesviruses
0 papillomaviruses
0 Viral metagenomics
0 Polyomaviruses
0 Viral tumorigenesis

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Article
Published: 03 August 2021
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The tumor microenvironment (TME) is a complex niche enveloping a tumor formed by extracellular matrix, blood vessels, immune cells, and fibroblasts constantly interacting with cancer cells. Although TME is increasingly recognized as a major player in cancer initiation and progression in many tumor types, its involvement in Merkel cell carcinoma (MCC) pathogenesis is currently unknown. Here, we provide the first molecular and functional characterization of cancer- associated fibroblasts (CAFs), the major TME component, in MCC patient-derived xenografts. We show that subcutaneous co-injection of patient-derived CAFs and human MCC MKL-1 cells into SCID mice significantly promotes tumor growth and metastasis. These fast-growing xenografts are characterized by areas densely populated with human CAFs, mainly localized around blood vessels. We also provide evidence that the growth-promoting activity of MCC-derived CAFs is mediated by the APA/Ang II-III/AT1R axis, with the expression of aminopeptidase A (APA) in CAFs being the upstream triggering event. Altogether, our findings point to APA as a potential marker for MCC prognostic stratification and a novel candidate therapeutic target.

ACS Style

Silvia Albertini; Licia Martuscelli; Cinzia Borgogna; Sanamjeet Virdi; Daniela Indenbirken; Irene Lo Cigno; Gloria Griffante; Federica Calati; Renzo Boldorini; Nicole Fischer; Marisa Gariglio. Cancer-associated fibroblasts exert a pro-angiogenic activity in Merkel cell carcinoma. 2021, 1 .

AMA Style

Silvia Albertini, Licia Martuscelli, Cinzia Borgogna, Sanamjeet Virdi, Daniela Indenbirken, Irene Lo Cigno, Gloria Griffante, Federica Calati, Renzo Boldorini, Nicole Fischer, Marisa Gariglio. Cancer-associated fibroblasts exert a pro-angiogenic activity in Merkel cell carcinoma. . 2021; ():1.

Chicago/Turabian Style

Silvia Albertini; Licia Martuscelli; Cinzia Borgogna; Sanamjeet Virdi; Daniela Indenbirken; Irene Lo Cigno; Gloria Griffante; Federica Calati; Renzo Boldorini; Nicole Fischer; Marisa Gariglio. 2021. "Cancer-associated fibroblasts exert a pro-angiogenic activity in Merkel cell carcinoma." , no. : 1.

Journal article
Published: 02 August 2021 in Computational Biology and Chemistry
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Next-generation sequencing is regularly used to identify viral sequences in DNA or RNA samples of infected hosts. A major step of most pipelines for virus detection is to map sequence reads against known virus genomes. Due to small differences between the sequences of related viruses, and due to several biological or technical errors, mapping underlies uncertainties. As a consequence, the resulting list of detected viruses can lack robustness. A new approach for generating artificial sequencing reads together with a strategy of resampling from the original findings is proposed that can help to assess the robustness of the originally identified list of viruses. From the original mapping result in form of a SAM file, a set of statistical distributions are derived. These are used in the resampling pipeline to generate new artificial reads which are again mapped versus the reference genomes. By summarizing the resampling procedure, the analyst receives information about whether the presence of a particular virus in the sample gains or losses evidence, and thus about the robustness of the original mapping list but also that of individual viruses in this list. To judge robustness, several indicators are derived from the resampling procedure such as the correlation between original and resampling read counts, or the statistical detection of outliers in the differences of read counts. Additionally, graphical illustrations of read count shifts via Sankey diagrams are provided. To demonstrate the use of the new approach, the resampling approach is applied to three real-world data samples, one of them with laboratory-confirmed Influenza sequences, and to artificially generated data where virus sequences have been spiked into the sequencing data of a host. By applying the resampling pipeline, several viruses drop from the original list while new viruses emerge, showing robustness of those viruses that remain in the list. The evaluation of the new approach shows that the resampling approach is helpful to analyze the viral content of a biological sample, to rate the robustness of original findings and to better show the overall distribution of findings. The method is also applicable to other virus detection pipelines based on read mapping.

ACS Style

Moritz Kohls; Babak Saremi; Ihsan Muchsin; Nicole Fischer; Paul Becher; Klaus Jung. A resampling strategy for studying robustness in virus detection pipelines. Computational Biology and Chemistry 2021, 94, 107555 .

AMA Style

Moritz Kohls, Babak Saremi, Ihsan Muchsin, Nicole Fischer, Paul Becher, Klaus Jung. A resampling strategy for studying robustness in virus detection pipelines. Computational Biology and Chemistry. 2021; 94 ():107555.

Chicago/Turabian Style

Moritz Kohls; Babak Saremi; Ihsan Muchsin; Nicole Fischer; Paul Becher; Klaus Jung. 2021. "A resampling strategy for studying robustness in virus detection pipelines." Computational Biology and Chemistry 94, no. : 107555.

Journal article
Published: 08 July 2021 in Journal of Clinical Virology
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Metagenomic sequencing is increasingly being used in clinical settings for difficult to diagnose cases. The performance of viral metagenomic protocols relies to a large extent on the bioinformatic analysis. In this study, the European Society for Clinical Virology (ESCV) Network on NGS (ENNGS) initiated a benchmark of metagenomic pipelines currently used in clinical virological laboratories. Metagenomic datasets from 13 clinical samples from patients with encephalitis or viral respiratory infections characterized by PCR were selected. The datasets were analyzed with 13 different pipelines currently used in virological diagnostic laboratories of participating ENNGS members. The pipelines and classification tools were: Centrifuge, DAMIAN, DIAMOND, DNASTAR, FEVIR, Genome Detective, Jovian, MetaMIC, MetaMix, One Codex, RIEMS, VirMet, and Taxonomer. Performance, characteristics, clinical use, and user-friendliness of these pipelines were analyzed. Overall, viral pathogens with high loads were detected by all the evaluated metagenomic pipelines. In contrast, lower abundance pathogens and mixed infections were only detected by 3/13 pipelines, namely DNASTAR, FEVIR, and MetaMix. Overall sensitivity ranged from 80% (10/13) to 100% (13/13 datasets). Overall positive predictive value ranged from 71-100%. The majority of the pipelines classified sequences based on nucleotide similarity (8/13), only a minority used amino acid similarity, and 6 of the 13 pipelines assembled sequences de novo. No clear differences in performance were detected that correlated with these classification approaches. Read counts of target viruses varied between the pipelines over a range of 2-3 log, indicating differences in limit of detection. A wide variety of viral metagenomic pipelines is currently used in the participating clinical diagnostic laboratories. Detection of low abundant viral pathogens and mixed infections remains a challenge, implicating the need for standardization and validation of metagenomic analysis for clinical diagnostic use. Future studies should address the selective effects due to the choice of different reference viral databases.

ACS Style

Jutte J.C. de Vries; Julianne R. Brown; Nicole Fischer; Igor A. Sidorov; Sofia Morfopoulou; Jiabin Huang; Bas B. Oude Munnink; Arzu Sayiner; Alihan Bulgurcu; Christophe Rodriguez; Guillaume Gricourt; Els Keyaerts; Leen Beller; Claudia Bachofen; Jakub Kubacki; Cordey Samuel; Laubscher Florian; Schmitz Dennis; Martin Beer; Dirk Hoeper; Michael Huber; Verena Kufner; Maryam Zaheri; Aitana Lebrand; Anna Papa; Sander van Boheemen; Aloys C.M. Kroes; Judith Breuer; F. Xavier Lopez-Labrador; Eric C.J. Claas. Benchmark of thirteen bioinformatic pipelines for metagenomic virus diagnostics using datasets from clinical samples. Journal of Clinical Virology 2021, 141, 104908 .

AMA Style

Jutte J.C. de Vries, Julianne R. Brown, Nicole Fischer, Igor A. Sidorov, Sofia Morfopoulou, Jiabin Huang, Bas B. Oude Munnink, Arzu Sayiner, Alihan Bulgurcu, Christophe Rodriguez, Guillaume Gricourt, Els Keyaerts, Leen Beller, Claudia Bachofen, Jakub Kubacki, Cordey Samuel, Laubscher Florian, Schmitz Dennis, Martin Beer, Dirk Hoeper, Michael Huber, Verena Kufner, Maryam Zaheri, Aitana Lebrand, Anna Papa, Sander van Boheemen, Aloys C.M. Kroes, Judith Breuer, F. Xavier Lopez-Labrador, Eric C.J. Claas. Benchmark of thirteen bioinformatic pipelines for metagenomic virus diagnostics using datasets from clinical samples. Journal of Clinical Virology. 2021; 141 ():104908.

Chicago/Turabian Style

Jutte J.C. de Vries; Julianne R. Brown; Nicole Fischer; Igor A. Sidorov; Sofia Morfopoulou; Jiabin Huang; Bas B. Oude Munnink; Arzu Sayiner; Alihan Bulgurcu; Christophe Rodriguez; Guillaume Gricourt; Els Keyaerts; Leen Beller; Claudia Bachofen; Jakub Kubacki; Cordey Samuel; Laubscher Florian; Schmitz Dennis; Martin Beer; Dirk Hoeper; Michael Huber; Verena Kufner; Maryam Zaheri; Aitana Lebrand; Anna Papa; Sander van Boheemen; Aloys C.M. Kroes; Judith Breuer; F. Xavier Lopez-Labrador; Eric C.J. Claas. 2021. "Benchmark of thirteen bioinformatic pipelines for metagenomic virus diagnostics using datasets from clinical samples." Journal of Clinical Virology 141, no. : 104908.

Communication
Published: 12 April 2021 in Viruses
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So far, only a few reports about reinfections with SARS-CoV-2 have been published, and they often lack detailed immunological and virological data. We report about a SARS-CoV-2 reinfection with a genetically distinct SARS-CoV-2 variant in an immunocompetent female healthcare worker that has led to a mild disease course. No obvious viral escape mutations were observed in the second virus variant. The infectious virus was shed from the patient during the second infection episode despite the presence of neutralizing antibodies in her blood. Our data indicate that a moderate immune response after the first infection, but not a viral escape, did allow for reinfection and live virus shedding.

ACS Style

Thomas Brehm; Susanne Pfefferle; Ronald von Possel; Robin Kobbe; Dominik Nörz; Stefan Schmiedel; Adam Grundhoff; Flaminia Olearo; Petra Emmerich; Alexis Robitaille; Thomas Günther; Platon Braun; Gabriele Andersen; Johannes Knobloch; Marylyn Addo; Ansgar Lohse; Martin Aepfelbacher; Nicole Fischer; Julian Schulze Zur Wiesch; Marc Lütgehetmann. SARS-CoV-2 Reinfection in a Healthcare Worker Despite the Presence of Detectable Neutralizing Antibodies. Viruses 2021, 13, 661 .

AMA Style

Thomas Brehm, Susanne Pfefferle, Ronald von Possel, Robin Kobbe, Dominik Nörz, Stefan Schmiedel, Adam Grundhoff, Flaminia Olearo, Petra Emmerich, Alexis Robitaille, Thomas Günther, Platon Braun, Gabriele Andersen, Johannes Knobloch, Marylyn Addo, Ansgar Lohse, Martin Aepfelbacher, Nicole Fischer, Julian Schulze Zur Wiesch, Marc Lütgehetmann. SARS-CoV-2 Reinfection in a Healthcare Worker Despite the Presence of Detectable Neutralizing Antibodies. Viruses. 2021; 13 (4):661.

Chicago/Turabian Style

Thomas Brehm; Susanne Pfefferle; Ronald von Possel; Robin Kobbe; Dominik Nörz; Stefan Schmiedel; Adam Grundhoff; Flaminia Olearo; Petra Emmerich; Alexis Robitaille; Thomas Günther; Platon Braun; Gabriele Andersen; Johannes Knobloch; Marylyn Addo; Ansgar Lohse; Martin Aepfelbacher; Nicole Fischer; Julian Schulze Zur Wiesch; Marc Lütgehetmann. 2021. "SARS-CoV-2 Reinfection in a Healthcare Worker Despite the Presence of Detectable Neutralizing Antibodies." Viruses 13, no. 4: 661.

Journal article
Published: 26 March 2021 in Journal of Clinical Virology
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Metagenomic next-generation sequencing (mNGS) is an untargeted technique for determination microbial DNA/RNA sequences in a variety of sample types from patients with infectious syndromes. mNGS is still in its early stages of broader translation into clinical application. To further support the development, implementation, optimization and standardization of mNGS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mNGS for viral diagnostics to share methodologies and experiences, and to develop application guidelines. Following the ENNGS publication Recommendations for the introduction of mNGS in clinical virology, part I: wet lab procedure in this journal, the current manuscript aims to provide practical recommendations for the bioinformatic analysis of mNGS data and reporting of results to clinicians.

ACS Style

Jutte J.C. de Vries; Julianne R. Brown; Natacha Couto; Martin Beer; Philippe Le Mercier; Igor Sidorov; Anna Papa; Nicole Fischer; Bas B. Oude Munnink; Christophe Rodriquez; Maryam Zaheri; Arzu Sayiner; Mario Hönemann; Alba Pérez-Cataluña; Ellen C. Carbo; Claudia Bachofen; Jakub Kubacki; Dennis Schmitz; Katerina Tsioka; Sébastien Matamoros; Dirk Höper; Marta Hernandez; Elisabeth Puchhammer-Stöckl; Aitana Lebrand; Michael Huber; Peter Simmonds; Eric C.J. Claas; F. Xavier López-Labrador. Recommendations for the introduction of metagenomic next-generation sequencing in clinical virology, part II: bioinformatic analysis and reporting. Journal of Clinical Virology 2021, 138, 104812 .

AMA Style

Jutte J.C. de Vries, Julianne R. Brown, Natacha Couto, Martin Beer, Philippe Le Mercier, Igor Sidorov, Anna Papa, Nicole Fischer, Bas B. Oude Munnink, Christophe Rodriquez, Maryam Zaheri, Arzu Sayiner, Mario Hönemann, Alba Pérez-Cataluña, Ellen C. Carbo, Claudia Bachofen, Jakub Kubacki, Dennis Schmitz, Katerina Tsioka, Sébastien Matamoros, Dirk Höper, Marta Hernandez, Elisabeth Puchhammer-Stöckl, Aitana Lebrand, Michael Huber, Peter Simmonds, Eric C.J. Claas, F. Xavier López-Labrador. Recommendations for the introduction of metagenomic next-generation sequencing in clinical virology, part II: bioinformatic analysis and reporting. Journal of Clinical Virology. 2021; 138 ():104812.

Chicago/Turabian Style

Jutte J.C. de Vries; Julianne R. Brown; Natacha Couto; Martin Beer; Philippe Le Mercier; Igor Sidorov; Anna Papa; Nicole Fischer; Bas B. Oude Munnink; Christophe Rodriquez; Maryam Zaheri; Arzu Sayiner; Mario Hönemann; Alba Pérez-Cataluña; Ellen C. Carbo; Claudia Bachofen; Jakub Kubacki; Dennis Schmitz; Katerina Tsioka; Sébastien Matamoros; Dirk Höper; Marta Hernandez; Elisabeth Puchhammer-Stöckl; Aitana Lebrand; Michael Huber; Peter Simmonds; Eric C.J. Claas; F. Xavier López-Labrador. 2021. "Recommendations for the introduction of metagenomic next-generation sequencing in clinical virology, part II: bioinformatic analysis and reporting." Journal of Clinical Virology 138, no. : 104812.

Journal article
Published: 04 February 2021 in Journal of Virological Methods
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In immunocompromised patients, BK Virus (BKV) reactivation may cause serious disease with high morbidity. Particularly for patient management after solid organ transplantation, monitoring of viral load in different clinical specimens is crucial to ensure early diagnosis and response to reactivation. In this study, we evaluated the clinical performance of a custom designed primer /probe set for detection of BKV on the cobas® 6800, a high-throughput platform, employing the open channel of the system for integration of a lab-developed test (LDT). A primer/probe set was optimized for the use on a high-throughput platform. Clinical performance was assessed in EDTA-plasma, serum and urine samples. Limit-of-detection (LOD) was determined by using a dilution series of BKV WHO standard. A CE-labeled PCR test (Altona Diagnostics) was used as a comparison to the assay. The LOD for the LDT BKV assay was 6.7 IU/mL. Inter-and intra-run variability (at 5 x LOD) was low (<1.5 Ct in all specimens). All quality control panel specimens (Instand Germany n = 19) were correctly identified. Of 290 clinical samples tested, results were concordant for 280 samples. Sensitivity and specificity of the assay were 96 % and 98 % respectively. The quantitative analysis revealed a strong correlation (linear regression) between the CE-labelled comparator assay and the new BKV LDT assay with r2 = 0.96 for n = 123 urine samples and r2 = 0.98 for n = 167 plasma/serum samples. Compared to a CE-IVD assay, the adapted LDT showed good analytical and clinical sensitivity and specificity for the detection and quantification of BKV in different clinical specimens. It represents a convenient solution to automate the LDT workflow with low hands-on time and thus facilitates high-throughput screening for BKV reactivation in immunocompromised patients.

ACS Style

Alice Fritzsche; Laura Berneking; Dominic Nörz; Svenja Reucher; Nicole Fischer; Hannes Roggenkamp; Martin Aepfelbacher; Holger Rohde; Susanne Pfefferle; Marc Lütgehetmann. Clinical evaluation of a laboratory-developed quantitative BK virus-PCR assay using the cobas® omni Utility Channel. Journal of Virological Methods 2021, 290, 114093 .

AMA Style

Alice Fritzsche, Laura Berneking, Dominic Nörz, Svenja Reucher, Nicole Fischer, Hannes Roggenkamp, Martin Aepfelbacher, Holger Rohde, Susanne Pfefferle, Marc Lütgehetmann. Clinical evaluation of a laboratory-developed quantitative BK virus-PCR assay using the cobas® omni Utility Channel. Journal of Virological Methods. 2021; 290 ():114093.

Chicago/Turabian Style

Alice Fritzsche; Laura Berneking; Dominic Nörz; Svenja Reucher; Nicole Fischer; Hannes Roggenkamp; Martin Aepfelbacher; Holger Rohde; Susanne Pfefferle; Marc Lütgehetmann. 2021. "Clinical evaluation of a laboratory-developed quantitative BK virus-PCR assay using the cobas® omni Utility Channel." Journal of Virological Methods 290, no. : 114093.

Journal article
Published: 18 November 2020 in Journal of Clinical Virology
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Metagenomic high-throughput sequencing (mHTS) is a hypothesis-free, universal pathogen detection technique for determination of the DNA/RNA sequences in a variety of sample types and infectious syndromes. mHTS is still in its early stages of translating into clinical application. To support the development, implementation and standardization of mHTS procedures for virus diagnostics, the European Society for Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS) has been established. The aim of ENNGS is to bring together professionals involved in mHTS for viral diagnostics to share methodologies and experiences, and to develop application recommendations. This manuscript aims to provide practical recommendations for the wet lab procedures necessary for implementation of mHTS for virus diagnostics and to give recommendations for development and validation of laboratory methods, including mHTS quality assurance, control and quality assessment protocols.

ACS Style

F. Xavier López-Labrador; Julianne R. Brown; Nicole Fischer; Heli Harvala; Sander Van Boheemen; Ondrej Cinek; Arzu Sayiner; Tina Vasehus Madsen; Eeva Auvinen; Verena Kufner; Michael Huber; Christophe Rodriguez; Marcel Jonges; Mario Hönemann; Petri Susi; Hugo Sousa; Paul E. Klapper; Alba Pérez-Cataluňa; Marta Hernandez; Richard Molenkamp; Lia van der Hoek; Rob Schuurman; Natacha Couto; Karoline Leuzinger; Peter Simmonds; Martin Beer; Dirk Höper; Sergio Kamminga; Mariet C.W. Feltkamp; Jesús Rodríguez-Díaz; Els Keyaerts; Xiaohui Chen Nielsen; Elisabeth Puchhammer-Stöckl; Aloys C.M. Kroes; Javier Buesa; Judy Breuer; Eric C.J. Claas; Jutte J.C. de Vries. Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I: Wet lab procedure. Journal of Clinical Virology 2020, 134, 104691 .

AMA Style

F. Xavier López-Labrador, Julianne R. Brown, Nicole Fischer, Heli Harvala, Sander Van Boheemen, Ondrej Cinek, Arzu Sayiner, Tina Vasehus Madsen, Eeva Auvinen, Verena Kufner, Michael Huber, Christophe Rodriguez, Marcel Jonges, Mario Hönemann, Petri Susi, Hugo Sousa, Paul E. Klapper, Alba Pérez-Cataluňa, Marta Hernandez, Richard Molenkamp, Lia van der Hoek, Rob Schuurman, Natacha Couto, Karoline Leuzinger, Peter Simmonds, Martin Beer, Dirk Höper, Sergio Kamminga, Mariet C.W. Feltkamp, Jesús Rodríguez-Díaz, Els Keyaerts, Xiaohui Chen Nielsen, Elisabeth Puchhammer-Stöckl, Aloys C.M. Kroes, Javier Buesa, Judy Breuer, Eric C.J. Claas, Jutte J.C. de Vries. Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I: Wet lab procedure. Journal of Clinical Virology. 2020; 134 ():104691.

Chicago/Turabian Style

F. Xavier López-Labrador; Julianne R. Brown; Nicole Fischer; Heli Harvala; Sander Van Boheemen; Ondrej Cinek; Arzu Sayiner; Tina Vasehus Madsen; Eeva Auvinen; Verena Kufner; Michael Huber; Christophe Rodriguez; Marcel Jonges; Mario Hönemann; Petri Susi; Hugo Sousa; Paul E. Klapper; Alba Pérez-Cataluňa; Marta Hernandez; Richard Molenkamp; Lia van der Hoek; Rob Schuurman; Natacha Couto; Karoline Leuzinger; Peter Simmonds; Martin Beer; Dirk Höper; Sergio Kamminga; Mariet C.W. Feltkamp; Jesús Rodríguez-Díaz; Els Keyaerts; Xiaohui Chen Nielsen; Elisabeth Puchhammer-Stöckl; Aloys C.M. Kroes; Javier Buesa; Judy Breuer; Eric C.J. Claas; Jutte J.C. de Vries. 2020. "Recommendations for the introduction of metagenomic high-throughput sequencing in clinical virology, part I: Wet lab procedure." Journal of Clinical Virology 134, no. : 104691.

Journal article
Published: 27 October 2020 in EMBO Molecular Medicine
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We describe a multifactorial investigation of a SARS-CoV-2 outbreak in a large meat processing complex in Germany. Infection event timing, spatial, climate and ventilation conditions in the processing plant, sharing of living quarters and transport, and viral genome sequences were analyzed. Our results suggest that a single index case transmitted SARS-CoV-2 to co-workers over distances of more than 8 m, within a confined work area in which air is constantly recirculated and cooled. Viral genome sequencing shows that all cases share a set of mutations representing a novel sub-branch in the SARS-CoV-2 C20 clade. We identified the same set of mutations in samples collected in the time period between this initial infection cluster and a subsequent outbreak within the same factory, with the largest number of confirmed SARS-CoV-2 cases in a German meat processing facility reported so far. Our results indicate climate conditions, fresh air exchange rates, and airflow as factors that can promote efficient spread of SARS-CoV-2 via long distances and provide insights into possible requirements for pandemic mitigation strategies in industrial workplace settings.

ACS Style

Thomas Günther; Manja Czech‐Sioli; Daniela Indenbirken; Alexis Robitaille; Peter Tenhaken; Martin Exner; Matthias Ottinger; Nicole Fischer; Adam Grundhoff; Melanie M Brinkmann. SARS‐CoV‐2 outbreak investigation in a German meat processing plant. EMBO Molecular Medicine 2020, 12, e13296 .

AMA Style

Thomas Günther, Manja Czech‐Sioli, Daniela Indenbirken, Alexis Robitaille, Peter Tenhaken, Martin Exner, Matthias Ottinger, Nicole Fischer, Adam Grundhoff, Melanie M Brinkmann. SARS‐CoV‐2 outbreak investigation in a German meat processing plant. EMBO Molecular Medicine. 2020; 12 (12):e13296.

Chicago/Turabian Style

Thomas Günther; Manja Czech‐Sioli; Daniela Indenbirken; Alexis Robitaille; Peter Tenhaken; Martin Exner; Matthias Ottinger; Nicole Fischer; Adam Grundhoff; Melanie M Brinkmann. 2020. "SARS‐CoV‐2 outbreak investigation in a German meat processing plant." EMBO Molecular Medicine 12, no. 12: e13296.

Preprint content
Published: 12 October 2020
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Stroke and central nervous system dysfunction are cardinal symptoms in critically ill corona virus disease 19 (COVID-19) patients. In an autopsy series of 32 COVID-19 patients, we investigated whether carotid arteries were infected with SARS-CoV-2 by employing genomic, virologic, histochemical and transcriptomic analyses. We show that SARS-CoV-2 productively infects and modulates vascular responses in carotid arteries. This finding has far reaching implications for the understanding and clinical treatment of COVID-19.

ACS Style

Susanne Pfefferle; Thomas Guenther; Victor Puelles; Fabian Heinrich; Dominik Noerz; Manja Czech-Sioli; Alexander Carstens; Susanne Krasemann; Milagros Wong; Lisa Oestereich; Tim Magnus; Lena Allweiss; Caroline Edler; Ann-Sophie Schroeder; Maura Dandri; Tobias Huber; Markus Glatzel; Klaus Pueschel; Adam Grundhoff; Marc Luetgehetmann; Martin Aepfelbacher; Nicole Fischer. SARS-CoV-2 infects carotid arteries: implications for vascular disease and organ injury in COVID-19. 2020, 1 .

AMA Style

Susanne Pfefferle, Thomas Guenther, Victor Puelles, Fabian Heinrich, Dominik Noerz, Manja Czech-Sioli, Alexander Carstens, Susanne Krasemann, Milagros Wong, Lisa Oestereich, Tim Magnus, Lena Allweiss, Caroline Edler, Ann-Sophie Schroeder, Maura Dandri, Tobias Huber, Markus Glatzel, Klaus Pueschel, Adam Grundhoff, Marc Luetgehetmann, Martin Aepfelbacher, Nicole Fischer. SARS-CoV-2 infects carotid arteries: implications for vascular disease and organ injury in COVID-19. . 2020; ():1.

Chicago/Turabian Style

Susanne Pfefferle; Thomas Guenther; Victor Puelles; Fabian Heinrich; Dominik Noerz; Manja Czech-Sioli; Alexander Carstens; Susanne Krasemann; Milagros Wong; Lisa Oestereich; Tim Magnus; Lena Allweiss; Caroline Edler; Ann-Sophie Schroeder; Maura Dandri; Tobias Huber; Markus Glatzel; Klaus Pueschel; Adam Grundhoff; Marc Luetgehetmann; Martin Aepfelbacher; Nicole Fischer. 2020. "SARS-CoV-2 infects carotid arteries: implications for vascular disease and organ injury in COVID-19." , no. : 1.

Research note
Published: 29 September 2020 in Clinical Microbiology and Infection
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Objectives Investigation whether in depth characterization of virus variant patterns can be used for epidemiological analysis of the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection clusters in Hamburg, Germany. Methods Metagenomic RNA-sequencing and amplicon-sequencing and subsequent variant calling in 25 respiratory samples from SARS-CoV-2 infected patients involved in the earliest infection clusters in Hamburg. Results Amplikon sequencing and cluster analyses of these SARS-CoV-2 sequences allowed the identification of the first infection cluster and five non-related infection clusters occurring at the beginning of the viral entry of SARS-CoV-2 in the Hamburg metropolitan region. Viral genomics together with epidemiological analyses revealed that the index patient acquired the infection in northern Italy and transmitted it to two out of 134 contacts. Single nucleotide polymorphisms clearly distinguished the virus variants of the index and other clusters and allowed us to track in which sequences worldwide these mutations were first described. Minor variant analyses identified the transmission of intra-host variants in the index cluster and household clusters. Conclusions SARS-CoV-2 variant tracing allows the identification of infection clusters and the follow up of infection chains occurring in the population. Furthermore, the follow up of minor viral variants in infection clusters can provide further resolution on transmission events indistinguishable at a consensus sequence level.

ACS Style

Susanne Pfefferle; Thomas Günther; Robin Kobbe; Manja Czech-Sioli; Dominic Nörz; René Santer; Jun Oh; Stefan Kluge; Lisa Oestereich; Kersten Peldschus; Daniela Indenbirken; Jiabin Huang; Adam Grundhoff; Martin Aepfelbacher; Johannes K. Knobloch; Marc Lütgehetmann; Nicole Fischer. SARS Coronavirus-2 variant tracing within the first Coronavirus Disease 19 clusters in northern Germany. Clinical Microbiology and Infection 2020, 27, 130.e5 -130.e8.

AMA Style

Susanne Pfefferle, Thomas Günther, Robin Kobbe, Manja Czech-Sioli, Dominic Nörz, René Santer, Jun Oh, Stefan Kluge, Lisa Oestereich, Kersten Peldschus, Daniela Indenbirken, Jiabin Huang, Adam Grundhoff, Martin Aepfelbacher, Johannes K. Knobloch, Marc Lütgehetmann, Nicole Fischer. SARS Coronavirus-2 variant tracing within the first Coronavirus Disease 19 clusters in northern Germany. Clinical Microbiology and Infection. 2020; 27 (1):130.e5-130.e8.

Chicago/Turabian Style

Susanne Pfefferle; Thomas Günther; Robin Kobbe; Manja Czech-Sioli; Dominic Nörz; René Santer; Jun Oh; Stefan Kluge; Lisa Oestereich; Kersten Peldschus; Daniela Indenbirken; Jiabin Huang; Adam Grundhoff; Martin Aepfelbacher; Johannes K. Knobloch; Marc Lütgehetmann; Nicole Fischer. 2020. "SARS Coronavirus-2 variant tracing within the first Coronavirus Disease 19 clusters in northern Germany." Clinical Microbiology and Infection 27, no. 1: 130.e5-130.e8.

Research article
Published: 24 August 2020 in PLOS Pathogens
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Merkel Cell Polyomavirus (MCPyV) is the etiological agent of the majority of Merkel Cell Carcinomas (MCC). MCPyV positive MCCs harbor integrated, defective viral genomes that constitutively express viral oncogenes. Which molecular mechanisms promote viral integration, if distinct integration patterns exist, and if integration occurs preferentially at loci with specific chromatin states is unknown. We here combined short and long-read (nanopore) next-generation sequencing and present the first high-resolution analysis of integration site structure in MCC cell lines as well as primary tumor material. We find two main types of integration site structure: Linear patterns with chromosomal breakpoints that map closely together, and complex integration loci that exhibit local amplification of genomic sequences flanking the viral DNA. Sequence analysis suggests that linear patterns are produced during viral replication by integration of defective/linear genomes into host DNA double strand breaks via non-homologous end joining, NHEJ. In contrast, our data strongly suggest that complex integration patterns are mediated by microhomology-mediated break-induced replication, MMBIR. Furthermore, we show by ChIP-Seq and RNA-Seq analysis that MCPyV preferably integrates in open chromatin and provide evidence that viral oncogene expression is driven by the viral promoter region, rather than transcription from juxtaposed host promoters. Taken together, our data explain the characteristics of MCPyV integration and may also provide a model for integration of other oncogenic DNA viruses such as papillomaviruses. Integration of viral DNA into the host genome is a key event in the pathogenesis of many virus-induced cancers. One such cancer is Merkel cell carcinoma (MCC), a highly malignant tumor that harbors monoclonally integrated and replication-defective Merkel cell polyomavirus (MCPyV) genomes. Although MCPyV integration sites have been analyzed before, there is very little knowledge of the mechanisms that lead to mutagenesis and integration of viral genomes. We used multiple sequencing technologies and interrogation of chromatin states to perform a comprehensive characterization of MCPyV integration loci. This analysis allowed us to deduce the events that likely precede viral integration. We provide evidence that the mutations which result in the replication defective phenotype are acquired prior to integration and propose that the cellular DNA repair pathways non-homologous end joining (NHEJ) and microhomology-mediated break-induced replication (MMBIR) produce two principal MCPyV integration patterns (simple and complex, respectively). We show that, although MCPyV integrates predominantly in open chromatin regions, viral oncogene expression is independent of host promoters and driven by the viral promotor region. Our findings are important since they can explain the mechanisms of MCPyV integration. Furthermore, our model may also apply to papillomaviruses, another clinically important family of oncogenic DNA viruses.

ACS Style

Manja Czech-Sioli; Thomas Günther; Marlin Therre; Michael Spohn; Daniela Indenbirken; Juliane Theiss; Sabine Riethdorf; Minyue Qi; Malik Alawi; Corinna Wülbeck; Irene Fernandez-Cuesta; Franziska Esmek; Jürgen C. Becker; Adam Grundhoff; Nicole Fischer. High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms. PLOS Pathogens 2020, 16, e1008562 .

AMA Style

Manja Czech-Sioli, Thomas Günther, Marlin Therre, Michael Spohn, Daniela Indenbirken, Juliane Theiss, Sabine Riethdorf, Minyue Qi, Malik Alawi, Corinna Wülbeck, Irene Fernandez-Cuesta, Franziska Esmek, Jürgen C. Becker, Adam Grundhoff, Nicole Fischer. High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms. PLOS Pathogens. 2020; 16 (8):e1008562.

Chicago/Turabian Style

Manja Czech-Sioli; Thomas Günther; Marlin Therre; Michael Spohn; Daniela Indenbirken; Juliane Theiss; Sabine Riethdorf; Minyue Qi; Malik Alawi; Corinna Wülbeck; Irene Fernandez-Cuesta; Franziska Esmek; Jürgen C. Becker; Adam Grundhoff; Nicole Fischer. 2020. "High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms." PLOS Pathogens 16, no. 8: e1008562.

Journal article
Published: 28 April 2020 in mBio
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We here describe Kap1 as a restriction factor in MCPyV infection. We report a novel, indirect mechanism by which Kap1 affects MCPyV replication. In contrast with from other DNA viruses, Kap1 does not associate with the viral genome in MCPyV infection and has no impact on viral gene expression. In MCPyV-infected nHDF cells, Kap1 phosphorylation (pKap1 S824) accumulates because of genomic stress mainly induced by viral DNA replication. In contrast, ectopic expression of LT or LT MCPyV mutants, previously shown to be important for induction of genotoxic stress, does not result in a similar extent of pKap1 accumulation. We show that cells actively replicating MCPyV accumulate pKap1 (in a manner dependent on the presence of ATM) and display a senescence phenotype reflected by G 2 arrest. These results are supported by transcriptome analyses showing that LT antigen, in a manner dependent on the presence of Kap1, induces expression of secreted factors, which is known as the senescence-associated secretory phenotype (SASP).

ACS Style

Svenja Siebels; Manja Czech-Sioli; Michael Spohn; Claudia Schmidt; Juliane Theiss; Daniela Indenbirken; Thomas Günther; Adam Grundhoff; Nicole Fischer. Merkel Cell Polyomavirus DNA Replication Induces Senescence in Human Dermal Fibroblasts in a Kap1/Trim28-Dependent Manner. mBio 2020, 11, 1 .

AMA Style

Svenja Siebels, Manja Czech-Sioli, Michael Spohn, Claudia Schmidt, Juliane Theiss, Daniela Indenbirken, Thomas Günther, Adam Grundhoff, Nicole Fischer. Merkel Cell Polyomavirus DNA Replication Induces Senescence in Human Dermal Fibroblasts in a Kap1/Trim28-Dependent Manner. mBio. 2020; 11 (2):1.

Chicago/Turabian Style

Svenja Siebels; Manja Czech-Sioli; Michael Spohn; Claudia Schmidt; Juliane Theiss; Daniela Indenbirken; Thomas Günther; Adam Grundhoff; Nicole Fischer. 2020. "Merkel Cell Polyomavirus DNA Replication Induces Senescence in Human Dermal Fibroblasts in a Kap1/Trim28-Dependent Manner." mBio 11, no. 2: 1.

Preprint content
Published: 23 April 2020
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Merkel Cell Polyomavirus (MCPyV) is the etiological agent of the majority of Merkel Cell Carcinomas (MCC). MCPyV positive MCCs harbor integrated, defective viral genomes that constitutively express viral oncogenes. Which molecular mechanisms promote viral integration, if distinct integration patterns exist, and if integration occurs preferentially at loci with specific chromatin states is unknown.We here combined short and long-read (nanopore) next-generation sequencing and present the first high-resolution analysis of integration site structure in MCC cell lines as well as primary tumor material. We find two main types of integration site structure: Linear patterns with chromosomal breakpoints that map closely together, and complex integration loci that exhibit local amplification of genomic sequences flanking the viral DNA. Sequence analysis suggests that linear patterns are produced during viral replication by integration of defective/linear genomes into host DNA double strand breaks via non-homologous end joining, NHEJ. In contrast, our data strongly suggest that complex integration patterns are mediated by microhomology-mediated break-induced replication, MMBIR.Furthermore, we show by ChIP-Seq and RNA-Seq analysis that MCPyV preferably integrates in open chromatin and provide evidence that viral oncogene expression is driven by the viral promoter region, rather than transcription from juxtaposed host promoters. Taken together, our data explain the characteristics of MCPyV integration and may also provide a model for integration of other oncogenic DNA viruses such as papillomaviruses.Author summaryIntegration of viral DNA into the host genome is a key event in the pathogenesis of many virus-induced cancers. One such cancer is Merkel cell carcinoma (MCC), a highly malignant tumor that harbors monoclonally integrated and replication-defective Merkel cell polyomavirus (MCPyV) genomes. Although MCPyV integration sites have been analyzed before, there is very little knowledge of the mechanisms that lead to mutagenesis and integration of viral genomes. We used multiple sequencing technologies and interrogation of chromatin states to perform a comprehensive characterization of MCPyV integration loci. This analysis allowed us to deduce the events that likely precede viral integration. We provide evidence that the mutations which result in the replication defective phenotype are acquired prior to integration and propose that the cellular DNA repair pathways non-homologous end joining (NHEJ) and microhomology-mediated break-induced replication (MMBIR) produce two principal MCPyV integration patterns (simple and complex, respectively). We show that, although MCPyV integrates predominantly in open chromatin regions, viral oncogene expression is independent of host promoters and driven by the viral promotor region. Our findings are important since they can explain the mechanisms of MCPyV integration. Furthermore, our model may also apply to papillomaviruses, another clinically important family of oncogenic DNA viruses.

ACS Style

Manja Czech-Sioli; Thomas Günther; Marlin Therre; Michael Spohn; Daniela Indenbirken; Juliane Theiss; Sabine Riethdorf; Minyue Qi; Malik Alawi; Corinna Wülbeck; Irene Fernandez-Cuesta; Franziska Esmek; Jürgen C. Becker; Adam Grundhoff; Nicole Fischer. High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms. 2020, 1 .

AMA Style

Manja Czech-Sioli, Thomas Günther, Marlin Therre, Michael Spohn, Daniela Indenbirken, Juliane Theiss, Sabine Riethdorf, Minyue Qi, Malik Alawi, Corinna Wülbeck, Irene Fernandez-Cuesta, Franziska Esmek, Jürgen C. Becker, Adam Grundhoff, Nicole Fischer. High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms. . 2020; ():1.

Chicago/Turabian Style

Manja Czech-Sioli; Thomas Günther; Marlin Therre; Michael Spohn; Daniela Indenbirken; Juliane Theiss; Sabine Riethdorf; Minyue Qi; Malik Alawi; Corinna Wülbeck; Irene Fernandez-Cuesta; Franziska Esmek; Jürgen C. Becker; Adam Grundhoff; Nicole Fischer. 2020. "High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms." , no. : 1.

Introduction
Published: 21 April 2020 in Seminars in Immunopathology
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Chen YL et al (2014) Nucleolin is important for Epstein-Barr virus nuclear antigen 1-mediated episome binding, maintenance, and transcription. Proc Natl Acad Sci U S A 111(1):243–248 De Leo A et al (2019) LANA oligomeric architecture is essential for KSHV nuclear body formation and viral genome maintenance during latency. PLoS Pathog 15(1):e1007489 Hellert J et al (2015) The 3D structure of Kaposi sarcoma herpesvirus LANA C-terminal domain bound to DNA. Proc Natl Acad Sci U S A 112(21):6694–6699 Woodard C, Shamay M, Liao G, Zhu J, Ng AN, Li R, Newman R, Rho HS, Hu J, Wan J, Qian J, Zhu H, Hayward SD (2012) Phosphorylation of the chromatin binding domain of KSHV LANA. PLoS Pathog 8(10):e1002972 Fitzsimmons L, Boyce AJ, Wei W, Chang C, Croom-Carter D, Tierney RJ, Herold MJ, Bell AI, Strasser A, Kelly GL, Rowe M (2018) Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells. Cell Death Differ 25(2):241–254 Richter-Larrea JA, Robles EF, Fresquet V, Beltran E, Rullan AJ, Agirre X, Calasanz MJ, Panizo C, Richter JA, Hernandez JM, Roman-Gomez J, Prosper F, Martinez-Climent JA (2010) Reversion of epigenetically mediated BIM silencing overcomes chemoresistance in Burkitt lymphoma. Blood 116(14):2531–2542 Cheeseman K, Weitzman JB (2015) Host-parasite interactions: an intimate epigenetic relationship. Cell Microbiol 17(8):1121–1132 Pinder M et al (1981) Proliferation and lymphocyte stimulatory capacity of Theileria-infected lymphoblastoid cells before and after the elimination of intracellular parasites. Immunology 44(1):51–60 Robert McMaster W, Morrison CJ, Kobor MS (2016) Epigenetics: a new model for intracellular parasite-host cell regulation. Trends Parasitol 32(7):515–521 Cheng AS, Li MS, Kang W, Cheng VY, Chou JL, Lau SS, Go MY, Lee CC, Ling TK, Ng EK, Yu J, Huang TH, To KF, Chan MW, Sung JJ, Chan FK (2013) Helicobacter pylori causes epigenetic dysregulation of FOXD3 to promote gastric carcinogenesis. Gastroenterology 144(1):122–133 e9 Padmanabhan N, Ushijima T, Tan P (2017) How to stomach an epigenetic insult: the gastric cancer epigenome. Nat Rev Gastroenterol Hepatol 14(8):467–478 Shin CM et al (2013) Changes in aberrant DNA methylation after Helicobacter pylori eradication: a long-term follow-up study. Int J Cancer 133(9):2034–2042 Burley M, Roberts S, Parish JL (2020) Epigenetic regulation of human papillomavirus transcription in the productive virus life cycle. Semin Immunopathol:1–13. https://doi.org/10.1007/s00281-019-00773-0 Buschle A, Hammscherschmidt W (2020) Epigenetic lifestyle of Epstein-Barr virus. Semin Immunopathol. https://doi.org/10.1007/s00281-020-00792-2 Dandri M (2020) Epigenetic modulation in chronic hepatitis B virus infection. Semin Immunopathol. https://doi.org/10.1007/s00281-020-00780-6 Froehlich J, Grundhoff A (2020) Epigenetic control in Kaposi sarcoma-associated herpesvirus infection and associated disease. Semin Immunopathol. https://doi.org/10.1007/s00281-020-00787-z Lange UC, Verdikt R, Ait-Ammar A, Lint C (2020) Epigenetic crosstalk in chronic infection with HIV-1. Semin Immunopathol:1–14. https://doi.org/10.1007/s00281-020-00783-3 Dong W, Hamon MA (2020) Revealing eukaryotic histone-modifying mechanisms through bacterial infection. Semin Immunopathol:1–13. https://doi.org/10.1007/s00281-019-00778-9 Villares M, Berthelet J, Weitzman JB (2020) The clever strategies used by intracellular parasites to hijack host gene expression. Semin Immunopathol:1–12. https://doi.org/10.1007/s00281-020-00779-z Download references Open Access funding provided by Projekt DEAL. Correspondence to Nicole Fischer. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This article is a contribution to the special issue on Infection-induced epigenetic changes and the pathogenesis of diseases - Guest Editor: Nicole Fischer Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Reprints and Permissions Fischer, N. Infection-induced epigenetic changes and their impact on the pathogenesis of diseases. Semin Immunopathol 42, 127–130 (2020). https://doi.org/10.1007/s00281-020-00793-1 Download citation Published: 21 April 2020 Issue Date: April 2020 DOI: https://doi.org/10.1007/s00281-020-00793-1

ACS Style

Nicole Fischer. Infection-induced epigenetic changes and their impact on the pathogenesis of diseases. Seminars in Immunopathology 2020, 42, 127 -130.

AMA Style

Nicole Fischer. Infection-induced epigenetic changes and their impact on the pathogenesis of diseases. Seminars in Immunopathology. 2020; 42 (2):127-130.

Chicago/Turabian Style

Nicole Fischer. 2020. "Infection-induced epigenetic changes and their impact on the pathogenesis of diseases." Seminars in Immunopathology 42, no. 2: 127-130.

Journal article
Published: 14 February 2020 in Journal of Virology
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MCPyV is the only human polyomavirus that is associated with cancer; the majority of Merkel cell cancers have a viral etiology. While much emphasis was placed on investigations to understand the transformation process by MCPyV oncoproteins and cellular factors, we have only limited knowledge of cellular factors participating in the MCPyV life cycle. Here, we describe Usp7, a cellular deubiquitination enzyme, as a new factor involved in MCPyV replication. Usp7 is known in the context of large DNA tumor viruses, Epstein-Barr virus (EBV) and Kaposi’s sarcoma herpesvirus, to restrict viral replication. Similar to EBV, where Usp7 binding to EBNA1 increases EBNA1 binding affinity to viral DNA, we find MCPyV LT binding to the origin of replication to be increased in the presence of Usp7, resulting in restriction of viral DNA replication. However, Usp7-induced restriction of MCPyV replication is independent of its enzymatic activity, thereby constituting a novel mechanism of Usp7-induced restriction of viral replication.

ACS Style

Manja Czech-Sioli; Svenja Siebels; Sonja Radau; René P. Zahedi; Claudia Schmidt; Thomas Dobner; Adam Grundhoff; Nicole Fischer. The Ubiquitin-Specific Protease Usp7, a Novel Merkel Cell Polyomavirus Large T-Antigen Interaction Partner, Modulates Viral DNA Replication. Journal of Virology 2020, 94, 1 .

AMA Style

Manja Czech-Sioli, Svenja Siebels, Sonja Radau, René P. Zahedi, Claudia Schmidt, Thomas Dobner, Adam Grundhoff, Nicole Fischer. The Ubiquitin-Specific Protease Usp7, a Novel Merkel Cell Polyomavirus Large T-Antigen Interaction Partner, Modulates Viral DNA Replication. Journal of Virology. 2020; 94 (5):1.

Chicago/Turabian Style

Manja Czech-Sioli; Svenja Siebels; Sonja Radau; René P. Zahedi; Claudia Schmidt; Thomas Dobner; Adam Grundhoff; Nicole Fischer. 2020. "The Ubiquitin-Specific Protease Usp7, a Novel Merkel Cell Polyomavirus Large T-Antigen Interaction Partner, Modulates Viral DNA Replication." Journal of Virology 94, no. 5: 1.

Journal article
Published: 14 November 2019 in Scientific Reports
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We describe DAMIAN, an open source bioinformatics tool designed for the identification of pathogenic microorganisms in diagnostic samples. By using authentic clinical samples and comparing our results to those from established analysis pipelines as well as conventional diagnostics, we demonstrate that DAMIAN rapidly identifies pathogens in different diagnostic entities, and accurately classifies viral agents down to the strain level. We furthermore show that DAMIAN is able to assemble full-length viral genomes even in samples co-infected with multiple virus strains, an ability which is of considerable advantage for the investigation of outbreak scenarios. While DAMIAN, similar to other pipelines, analyzes single samples to perform classification of sequences according to their likely taxonomic origin, it also includes a tool for cohort-based analysis. This tool uses cross-sample comparisons to identify sequence signatures that are frequently present in a sample group of interest (e.g., a disease-associated cohort), but occur less frequently in control cohorts. As this approach does not require homology searches in databases, it principally allows the identification of not only known, but also completely novel pathogens. Using samples from a meningitis outbreak, we demonstrate the feasibility of this approach in identifying enterovirus as the causative agent.

ACS Style

Malik Alawi; Lia Burkhardt; Daniela Indenbirken; Kerstin Reumann; Maximilian Christopeit; Nicolaus Kröger; Marc Lütgehetmann; Martin Aepfelbacher; Nicole Fischer; Adam Grundhoff. DAMIAN: an open source bioinformatics tool for fast, systematic and cohort based analysis of microorganisms in diagnostic samples. Scientific Reports 2019, 9, 16841 -17.

AMA Style

Malik Alawi, Lia Burkhardt, Daniela Indenbirken, Kerstin Reumann, Maximilian Christopeit, Nicolaus Kröger, Marc Lütgehetmann, Martin Aepfelbacher, Nicole Fischer, Adam Grundhoff. DAMIAN: an open source bioinformatics tool for fast, systematic and cohort based analysis of microorganisms in diagnostic samples. Scientific Reports. 2019; 9 (1):16841-17.

Chicago/Turabian Style

Malik Alawi; Lia Burkhardt; Daniela Indenbirken; Kerstin Reumann; Maximilian Christopeit; Nicolaus Kröger; Marc Lütgehetmann; Martin Aepfelbacher; Nicole Fischer; Adam Grundhoff. 2019. "DAMIAN: an open source bioinformatics tool for fast, systematic and cohort based analysis of microorganisms in diagnostic samples." Scientific Reports 9, no. 1: 16841-17.

Journal article
Published: 28 January 2019 in Viruses
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The proliferative darkening syndrome (PDS) is a lethal disease of brown trout (Salmo trutta fario) which occurs in several alpine Bavarian limestone rivers. Because mortality can reach 100%, PDS is a serious threat for affected fish populations. Recently, Kuehn and colleagues reported that a high throughput RNA sequencing approach identified a piscine orthoreovirus (PRV) as a causative agent of PDS. We investigated samples from PDS-affected fish obtained from two exposure experiments performed at the river Iller in 2008 and 2009. Using a RT-qPCR and a well-established next-generation RNA sequencing pipeline for pathogen detection, PRV-specific RNA was not detectable in PDS fish from 2009. In contrast, PRV RNA was readily detectable in several organs from diseased fish in 2008. However, similar virus loads were detectable in the control fish which were not exposed to Iller water and did not show any signs of the disease. Therefore, we conclude that PRV is not the causative agent of PDS of brown trout in the rhithral region of alpine Bavarian limestone rivers. The abovementioned study by Kuehn used only samples from the exposure experiment from 2008 and detected a subclinical PRV bystander infection. Work is ongoing to identify the causative agent of PDS.

ACS Style

Robert Fux; Daniela Arndt; Martin C. Langenmayer; Julia Schwaiger; Hermann Ferling; Nicole Fischer; Daniela Indenbirken; Adam Grundhoff; Lars Dölken; Mikolaj Adamek; Dieter Steinhagen; Gerd Sutter. Piscine Orthoreovirus 3 Is Not the Causative Pathogen of Proliferative Darkening Syndrome (PDS) of Brown Trout (Salmo trutta fario). Viruses 2019, 11, 112 .

AMA Style

Robert Fux, Daniela Arndt, Martin C. Langenmayer, Julia Schwaiger, Hermann Ferling, Nicole Fischer, Daniela Indenbirken, Adam Grundhoff, Lars Dölken, Mikolaj Adamek, Dieter Steinhagen, Gerd Sutter. Piscine Orthoreovirus 3 Is Not the Causative Pathogen of Proliferative Darkening Syndrome (PDS) of Brown Trout (Salmo trutta fario). Viruses. 2019; 11 (2):112.

Chicago/Turabian Style

Robert Fux; Daniela Arndt; Martin C. Langenmayer; Julia Schwaiger; Hermann Ferling; Nicole Fischer; Daniela Indenbirken; Adam Grundhoff; Lars Dölken; Mikolaj Adamek; Dieter Steinhagen; Gerd Sutter. 2019. "Piscine Orthoreovirus 3 Is Not the Causative Pathogen of Proliferative Darkening Syndrome (PDS) of Brown Trout (Salmo trutta fario)." Viruses 11, no. 2: 112.

Journal article
Published: 09 November 2018 in Journal of Autoimmunity
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Dysbiosis¸ i.e. changes in microbial composition at a mucosal interface, is implicated in the pathogenesis of many chronic inflammatory and autoimmune diseases. To assess the composition of the microbial upper respiratory tract (URT) community in patients with granulomatosis with polyangiitis (GPA), we used culture-independent high-throughput methods. In this prospective clinical study, nasal swabs were collected from patients with GPA, patients with rheumatoid arthritis (RA, disease control), and healthy controls. Nasal bacterial taxa were assessed using V3–V4 region 16S rRNA amplicon sequencing. Staphylococcus aureus, Haemophilus influenza, and entero- and rhinoviruses were detected using qPCR. Unbiased metagenomic RNA sequencing (UMERS) was performed in a subset of samples to determine the relative abundance of bacterial, fungal, and viral species. A trend toward reduced microbiome diversity was detected in GPA samples compared with healthy controls. The abundance of bacterial taxa and microbial richness were significantly decreased in GPA samples compared with RA samples. The relative abundance of bacterial families shifted, with increased Planococcaceae and decreased Moraxellaceae, Tissierellaceae, Staphylococcaceae, and Propionibacteriaceae in GPA and RA. Further, decreased abundance of Corynebacteriaceae, and Aerococcaceae was observed in GPA samples. Significantly more colonization of S. aureus was seen in the nasal microbiome of GPA compared with RA and healthy control samples. H. influenzae colonization was also observed in GPA samples. UMERS detected the presence of rhinoviral sequences in some GPA samples. Thus, our study uncovered changes in the URT microbial composition in patients with GPA and RA, suggesting that both immunosuppression and disease background affect the URT microbiome. Complex alterations of host-microbiome interactions in the URT could influence chronic endonasal inflammation in GPA.

ACS Style

Peter Lamprecht; Nicole Fischer; Jiabin Huang; Lia Burkhardt; Marc Lütgehetmann; Fabian Arndt; Ida Rolfs; Anja Kerstein; Christof Iking-Konert; Martin Laudien. Changes in the composition of the upper respiratory tract microbial community in granulomatosis with polyangiitis. Journal of Autoimmunity 2018, 97, 29 -39.

AMA Style

Peter Lamprecht, Nicole Fischer, Jiabin Huang, Lia Burkhardt, Marc Lütgehetmann, Fabian Arndt, Ida Rolfs, Anja Kerstein, Christof Iking-Konert, Martin Laudien. Changes in the composition of the upper respiratory tract microbial community in granulomatosis with polyangiitis. Journal of Autoimmunity. 2018; 97 ():29-39.

Chicago/Turabian Style

Peter Lamprecht; Nicole Fischer; Jiabin Huang; Lia Burkhardt; Marc Lütgehetmann; Fabian Arndt; Ida Rolfs; Anja Kerstein; Christof Iking-Konert; Martin Laudien. 2018. "Changes in the composition of the upper respiratory tract microbial community in granulomatosis with polyangiitis." Journal of Autoimmunity 97, no. : 29-39.

Journal article
Published: 01 July 2018 in Virology
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With the advent of new molecular tools, the discovery of new papillomaviruses (PVs) has accelerated during the past decade, enabling the expansion of knowledge about the viral populations that inhabit the human body. Human PVs (HPVs) are etiologically linked to benign or malignant lesions of the skin and mucosa. The detection of HPV types can vary widely, depending mainly on the methodology and the quality of the biological sample. Next-generation sequencing is one of the most powerful tools, enabling the discovery of novel viruses in a wide range of biological material. Here, we report a novel protocol for the detection of known and unknown HPV types in human skin and oral gargle samples using improved PCR protocols combined with next-generation sequencing. We identified 105 putative new PV types in addition to 296 known types, thus providing important information about the viral distribution in the oral cavity and skin.

ACS Style

Rosario N. Brancaccio; Alexis Robitaille; Sankhadeep Dutta; Cyrille Cuenin; Daiga Santare; Girts Skenders; Marcis Leja; Nicole Fischer; Anna R. Giuliano; Dana E. Rollison; Adam Grundhoff; Massimo Tommasino; Tarik Gheit. Generation of a novel next-generation sequencing-based method for the isolation of new human papillomavirus types. Virology 2018, 520, 1 -10.

AMA Style

Rosario N. Brancaccio, Alexis Robitaille, Sankhadeep Dutta, Cyrille Cuenin, Daiga Santare, Girts Skenders, Marcis Leja, Nicole Fischer, Anna R. Giuliano, Dana E. Rollison, Adam Grundhoff, Massimo Tommasino, Tarik Gheit. Generation of a novel next-generation sequencing-based method for the isolation of new human papillomavirus types. Virology. 2018; 520 ():1-10.

Chicago/Turabian Style

Rosario N. Brancaccio; Alexis Robitaille; Sankhadeep Dutta; Cyrille Cuenin; Daiga Santare; Girts Skenders; Marcis Leja; Nicole Fischer; Anna R. Giuliano; Dana E. Rollison; Adam Grundhoff; Massimo Tommasino; Tarik Gheit. 2018. "Generation of a novel next-generation sequencing-based method for the isolation of new human papillomavirus types." Virology 520, no. : 1-10.

Book chapter
Published: 10 March 2018 in Encyclopedia of AIDS
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Nicole Fischer; Adam Grundhoff. Merkel Cell Polyomavirus (MCV). Encyclopedia of AIDS 2018, 1326 -1333.

AMA Style

Nicole Fischer, Adam Grundhoff. Merkel Cell Polyomavirus (MCV). Encyclopedia of AIDS. 2018; ():1326-1333.

Chicago/Turabian Style

Nicole Fischer; Adam Grundhoff. 2018. "Merkel Cell Polyomavirus (MCV)." Encyclopedia of AIDS , no. : 1326-1333.