Publications

@article{nokey_66,

title = {Endogenous viral elements: insights into data availability and accessibility},

author = {Muriel Ritsch and Nadja Brait and Erin Harvey and Manja Marz and Sebastian Lequime},

doi = {10.1093/ve/veae099},

issn = {2057-1577},

year  = {2024},

date = {2024-11-23},

journal = {Virus Evolution},

volume = {10},

number = {1},

pages = {veae099},

abstract = {Endogenous viral elements (EVEs) are remnants of viral genetic material endogenized into the host genome. They have, in the last decades, attracted attention for their role as potential contributors to pathogenesis, drivers of selective advantage for the host, and genomic remnants of ancient viruses. EVEs have a nuanced and complex influence on both host health and evolution, and can offer insights on the deep evolutionary history of viruses. As an emerging field of research, several factors limit a comprehensive understanding of EVEs: they are currently underestimated and periodically overlooked in studies of the host genome, transcriptome, and virome. The absence of standardized guidelines for ensuring EVE-related data availability and accessibility following the FAIR (‘findable, accessible, interoperable, and reusable’) principles obstructs our ability to gather and connect information. Here, we discuss challenges to the availability and accessibility of EVE-related data and propose potential solutions. We identified the biological and research focus imbalance between different types of EVEs, and their overall biological complexity as genomic loci with viral ancestry, as potential challenges that can be addressed with the development of a user-oriented identification tool. In addition, reports of EVE identification are scattered between different subfields under different keywords, and EVE sequences and associated data are not properly gathered in databases. While developing an open and dedicated database might be ideal, targeted improvements of generalist databases might provide a pragmatic solution to EVE data and metadata accessibility. The implementation of these solutions, as well as the collective effort by the EVE scientific community in discussing and setting guidelines, is now drastically needed to lead the development of EVE research and offer insights into host–virus interactions and their evolutionary history.},

keywords = {evolution, phylogenetics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_66,

title = {Endogenous Bornavirus-like Elements in Bats: Evolutionary Insights from the Conserved Riboviral L-Gene in Microbats and Its Antisense Transcription in \textit{Myotis daubentonii}},

author = {Muriel Ritsch and Tom Eulenfeld and Kevin Lamkiewicz and Andreas Schoen and Friedemann Weber and Martin Hölzer and Manja Marz},

doi = {10.3390/v16081210},

issn = {1999-4915},

year  = {2024},

date = {2024-07-27},

urldate = {2024-07-27},

journal = {Viruses},

volume = {16},

issue = {8},

abstract = {Bats are ecologically diverse vertebrates characterized by their ability to host a wide range of viruses without apparent illness and the presence of numerous endogenous viral elements (EVEs). EVEs are well preserved, expressed, and may affect host biology and immunity, but their role in bat immune system evolution remains unclear. Among EVEs, endogenous bornavirus-like elements (EBLs) are bornavirus sequences integrated into animal genomes. Here, we identified a novel EBL in the microbat \textit{Myotis daubentonii}, EBLL-Cultervirus.10-MyoDau (short name is CV.10-MyoDau) that shows protein-level conservation with the L-protein of a \textit{Cultervirus} (Wuhan sharpbelly bornavirus). Surprisingly, we discovered a transcript on the antisense strand comprising three exons, which we named AMCR-MyoDau. The active transcription in \textit{Myotis daubentonii} tissues of AMCR-MyoDau, confirmed by RNA-Seq analysis and RT-PCR, highlights its potential role during viral infections. Using comparative genomics comprising 63 bat genomes, we demonstrate nucleotide-level conservation of CV.10-MyoDau and AMCR-MyoDau across various bat species and its detection in 22 \textit{Yangochiropera<i/> and 12 \textit{Yinpterochiroptera} species. To the best of our knowledge, this marks the first occurrence of a conserved EVE shared among diverse bat species, which is accompanied by a conserved antisense transcript. This highlights the need for future research to explore the role of EVEs in shaping the evolution of bat immunity.},

keywords = {evolution, phylogenetics, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_62,

title = {Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus},

author = {Sandra Triebel and Kevin Lamkiewicz and Nancy Ontiveros and Blake Sweeney and Peter F. Stadler and Anton I. Petrov and Michael Niepmann and Manja Marz},

doi = {10.1038/s41598-024-62897-0},

year  = {2024},

date = {2024-07-02},

urldate = {2024-07-02},

journal = {Scientific Reports},

volume = {14},

issue = {1},

abstract = {Hepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large ‘cloud’ of RNA genomes (quasispecies) which—by trial and error—comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape. In this context, it is important to identify which RNA secondary structures in the sequence space of the HCV genome are conserved, likely due to functional requirements. Here, we provide the first genome-wide multiple sequence alignment (MSA) with the prediction of RNA secondary structures throughout all representative full-length HCV genomes. We selected 57 representative genomes by clustering all complete HCV genomes from the BV-BRC database based on k-mer distributions and dimension reduction and adding RefSeq sequences. We include annotations of previously recognized features for easy comparison to other studies. Our results indicate that mainly the core coding region, the C-terminal NS5A region, and the NS5B region contain secondary structure elements that are conserved beyond coding sequence requirements, indicating functionality on the RNA level. In contrast, the genome regions in between contain less highly conserved structures. The results provide a complete description of all conserved RNA secondary structures and make clear that functionally important RNA secondary structures are present in certain HCV genome regions but are largely absent from other regions. Full-genome alignments of all branches of Hepacivirus C are provided in the supplement.},

keywords = {evolution, ncRNAs, phylogenetics, RNA structure, RNA-RNA interactions, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_47,

title = {The International Virus Bioinformatics Meeting 2023},

author = {Franziska Hufsky and Ana B. Abecasis and Artem Babaian and Sebastian Beck and Liam Brierley and Simon Dellicour and Christian Eggeling and Santiago F. Elena and Udo Gieraths and Anh D. Ha and Will Harvey and Terry C. Jones and Kevin Lamkiewicz and Gabriel L. Lovate and Dominik Lücking and Martin Machyna and Luca Nishimura and Maximilian K. Nocke and Bernard Y. Renard and Shoichi Sakaguchi and Lygeri Sakellaridi and Jannes Spangenberg and Maria Tarradas-Alemany and Sandra Triebel and Yulia Vakulenko and Rajitha Yasas Wijesekara and Fernando González-Candelas and Sarah Krautwurst and Alba Pérez-Cataluña and Walter Randazzo and Gloria Sánchez and Manja Marz},

doi = {10.3390/v15102031},

issn = {1999-4915},

year  = {2023},

date = {2023-09-30},

urldate = {2023-09-30},

journal = {Viruses},

volume = {15},

issue = {10},

abstract = {The 2023 International Virus Bioinformatics Meeting was held in Valencia, Spain, from 24–26 May 2023, attracting approximately 180 participants worldwide. The primary objective of the conference was to establish a dynamic scientific environment conducive to discussion, collaboration, and the generation of novel research ideas. As the first in-person event following the SARS-CoV-2 pandemic, the meeting facilitated highly interactive exchanges among attendees. It served as a pivotal gathering for gaining insights into the current status of virus bioinformatics research and engaging with leading researchers and emerging scientists. The event comprised eight invited talks, 19 contributed talks, and 74 poster presentations across eleven sessions spanning three days. Topics covered included machine learning, bacteriophages, virus discovery, virus classification, virus visualization, viral infection, viromics, molecular epidemiology, phylodynamic analysis, RNA viruses, viral sequence analysis, viral surveillance, and metagenomics. This report provides rewritten abstracts of the presentations, a summary of the key research findings, and highlights shared during the meeting.},

keywords = {annotation, software, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Hufsky2022,

title = {The International Virus Bioinformatics Meeting 2022},

author = {Franziska Hufsky and Denis Beslic and Dimitri Boeckaerts and Sebastian Duchene and Enrique González-Tortuero and Andreas J Gruber and Jiarong Guo and Daan Jansen and John Juma and Kunaphas Kongkitimanon and Antoni Luque and Muriel Ritsch and Gabriel L. Lovate and Luca Nishimura and Célia Pas and Esteban Domingo and Emma Hodcroft and Philippe Lemey and Matthew B Sullivan and Friedemann Weber and Fernando González-Candelas and Sarah Krautwurst and Alba Pérez-Cataluña and Walter Randazzo and Gloria Sánchez and Manja Marz },

doi = {10.3390/v14050973},

year  = {2022},

date = {2022-05-05},

urldate = {2022-05-05},

journal = {Viruses},

volume = {14},

issue = {5},

pages = {973},

abstract = {The International Virus Bioinformatics Meeting 2022 took place online, on 23-25 March 2022, and has attracted about 380 participants from all over the world. The goal of the meeting was to provide a meaningful and interactive scientific environment to promote discussion and collaboration and to inspire and suggest new research directions and questions. The participants created a highly interactive scientific environment even without physical face-to-face interactions. This meeting is a focal point to gain an insight into the state-of-the-art of the virus bioinformatics research landscape and to interact with researchers in the forefront as well as aspiring young scientists. The meeting featured eight invited and 18 contributed talks in eight sessions on three days, as well as 52 posters, which were presented during three virtual poster sessions. The main topics were: SARS-CoV-2, viral emergence and surveillance, virus-host interactions, viral sequence analysis, virus identification and annotation, phages, and viral diversity. This report summarizes the main research findings and highlights presented at the meeting.},

keywords = {annotation, software, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Gib mir den Virus und ich sag dir den Wirt},

author = {Franziska Hufsky and Manja Marz},

doi = {10.1007/s12268-022-1732-7},

year  = {2022},

date = {2022-03-28},

journal = {BIOSpektrum},

volume = {28},

pages = {225–226},

keywords = {software, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis},

author = {Daniel Wendisch and Oliver Dietrich and Tommaso Mari and Saskia von Stillfried and Ignacio L. Ibarra and Mirja Mittermaier and Christin Mache and Robert Lorenz Chua and Rainer Knoll and Sara Timm and Sophia Brumhard and Tobias Krammer and Henrik Zauber and Anna Luisa Hiller and Anna Pascual-Reguant and Ronja Mothes and Roman David Bülow and Jessica Schulze and Alexander M. Leipold and Sonja Djudjaj and Florian Erhard and Robert Geffers and Fabian Pott and Julia Kazmierski and Josefine Radke and Panagiotis Pergantis and Kevin Baßler and Claudia Conrad and Anna C. Aschenbrenner and Birgit Sawitzki and Markus Landthaler and Emanuel Wyler and David Horst and Deutsche COVID-19 OMICS Initiative (DeCOI) and Stefan Hippenstiel and Andreas Hocke and Frank L. Heppner and Alexander Uhrig and Carmen Garcia and Felix Machleidt and Susanne Herold and Sefer Elezkurtaj and Charlotte Thibeault and Martin Witzenrath and Clément Cochain and Norbert Suttorp and Christian Drosten and Christine Goffinet and Florian Kurth and Joachim L. Schultze and Helena Radbruch and Matthias Ochs and Roland Eils and Holger Müller-Redetzky and Anja E. Hauser and Malte D. Luecken and Fabian J. Theis and Christian Conrad and Thorsten Wolff and Peter Boor and Matthias Selbach and Antoine-Emmanuel Saliba and Leif Erik Sander},

doi = {10.1016/j.cell.2021.11.033},

year  = {2021},

date = {2021-12-22},

journal = {Cell},

volume = {184},

number = {26},

pages = { 6243-6261},

abstract = {COVID-19-induced "acute respiratory distress syndrome" (ARDS) is associated with prolonged respiratory failure and high mortality, but the mechanistic basis of lung injury remains incompletely understood. Here, we analyze pulmonary immune responses and lung pathology in two cohorts of patients with COVID-19 ARDS using functional single-cell genomics, immunohistology, and electron microscopy. We describe an accumulation of CD163-expressing monocyte-derived macrophages that acquired a profibrotic transcriptional phenotype during COVID-19 ARDS. Gene set enrichment and computational data integration revealed a significant similarity between COVID-19-associated macrophages and profibrotic macrophage populations identified in idiopathic pulmonary fibrosis. COVID-19 ARDS was associated with clinical, radiographic, histopathological, and ultrastructural hallmarks of pulmonary fibrosis. Exposure of human monocytes to SARS-CoV-2, but not influenza A virus or viral RNA analogs, was sufficient to induce a similar profibrotic phenotype in vitro. In conclusion, we demonstrate that SARS-CoV-2 triggers profibrotic macrophage responses and pronounced fibroproliferative ARDS.},

keywords = {coronavirus, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Goettsch:21,

title = {ITN—VIROINF: Understanding (Harmful) Virus-Host Interactions by Linking Virology and Bioinformatics},

author = {Winfried Göttsch and Niko Beerenwinkel and Li Deng and Lars Dölken and Bas E. Dutilh and Florian Erhard and Lars Kaderali and Max Kleist and Roland Marquet and Jelle Matthijnssens and Shawna McCallin and Dino McMahon and Thomas Rattei and Ronald P. Van Rij and David L. Robertson and Martin Schwemmle and Noam Stern-Ginossar and Manja Marz},

doi = {10.3390/v13050766},

year  = {2021},

date = {2021-04-27},

urldate = {2021-04-27},

journal = {Viruses},

volume = {13},

number = {5},

pages = {766},

publisher = {MDPI AG},

abstract = {Many recent studies highlight the fundamental importance of viruses. Besides their important role as human and animal pathogens, their beneficial, commensal or harmful functions are poorly understood. By developing and applying tailored bioinformatical tools in important virological models, the Marie Skłodowska-Curie Initiative International Training Network VIROINF will provide a better understanding of viruses and the interaction with their hosts. This will open the door to validate methods of improving viral growth, morphogenesis and development, as well as to control strategies against unwanted microorganisms. The key feature of VIROINF is its interdisciplinary nature, which brings together virologists and bioinformaticians to achieve common goals. },

keywords = {review, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Collatz:20,

title = {EpiDope: A Deep Neural Network for linear B-cell epitope prediction},

author = {Maximilian Collatz and Florian Mock and Emanuel Barth and Martin Hölzer and Konrad Sachse and Manja Marz},

editor = {Lenore Cowen},

url = {https://github.com/rnajena/EpiDope},

doi = {10.1093/bioinformatics/btaa773},

year  = {2020},

date = {2020-09-11},

urldate = {2020-09-11},

journal = {Bioinformatics},

volume = {37},

number = {4},

pages = {448–455},

publisher = {Oxford University Press (OUP)},

abstract = {By binding to specific structures on antigenic proteins, the so-called epitopes, B-cell antibodies can neutralize pathogens. The identification of B-cell epitopes is of great value for the development of specific serodiagnostic assays and the optimization of medical therapy. However, identifying diagnostically or therapeutically relevant epitopes is a challenging task that usually involves extensive laboratory work. In this study, we show that the time, cost and labor-intensive process of epitope detection in the lab can be significantly reduced using in silico prediction.

Here, we present EpiDope, a python tool which uses a deep neural network to detect linear B-cell epitope regions on individual protein sequences. With an area under the curve between 0.67 ± 0.07 in the receiver operating characteristic curve, EpiDope exceeds all other currently used linear B-cell epitope prediction tools. Our software is shown to reliably predict linear B-cell epitopes of a given protein sequence, thus contributing to a significant reduction of laboratory experiments and costs required for the conventional approach.},

keywords = {machine learning, software, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Mock:20,

title = {VIDHOP, viral host prediction with Deep Learning},

author = {Florian Mock and Adrian Viehweger and Emanuel Barth and Manja Marz},

editor = {Jinbo Xu},

url = {https://github.com/rnajena/vidhop},

doi = {10.1093/bioinformatics/btaa705},

year  = {2020},

date = {2020-08-10},

urldate = {2020-08-10},

journal = {Bioinformatics},

volume = {37},

number = {3},

pages = {318–325},

publisher = {Oxford University Press (OUP)},

abstract = {Zoonosis, the natural transmission of infections from animals to humans, is a far-reaching global problem. The recent outbreaks of Zikavirus, Ebolavirus and Coronavirus are examples of viral zoonosis, which occur more frequently due to globalization. In case of a virus outbreak, it is helpful to know which host organism was the original carrier of the virus to prevent further spreading of viral infection. Recent approaches aim to predict a viral host based on the viral genome, often in combination with the potential host genome and arbitrarily selected features. These methods are limited in the number of different hosts they can predict or the accuracy of the prediction.

Here, we present a fast and accurate deep learning approach for viral host prediction, which is based on the viral genome sequence only. We tested our deep neural network (DNN) on three different virus species (influenza A virus, rabies lyssavirus and rotavirus A). We achieved for each virus species an AUC between 0.93 and 0.98, allowing highly accurate predictions while using only fractions (100–400 bp) of the viral genome sequences. We show that deep neural networks are suitable to predict the host of a virus, even with a limited amount of sequences and highly unbalanced available data. The trained DNNs are the core of our virus–host prediction tool VIrus Deep learning HOst Prediction (VIDHOP). VIDHOP also allows the user to train and use models for other viruses.},

keywords = {machine learning, software, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Mostajo:20,

title = {A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes},

author = {Nelly F. Mostajo and Marie Lataretu and Sebastian Krautwurst and Florian Mock and Daniel Desirò and Kevin Lamkiewicz and Maximilian Collatz and Andreas Schoen and Friedemann Weber and Manja Marz and Martin Hölzer},

url = {https://www.rna.uni-jena.de/supplements/bats/index.html},

doi = {10.1093/nargab/lqz006},

year  = {2019},

date = {2019-09-30},

urldate = {2019-09-30},

journal = {NAR Genomics Bioinf},

volume = {2},

number = {1},

pages = {lqz006},

abstract = {Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies, we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and lncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (rna.uni-jena.de/supplements/bats) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology and important host–virus interactions.},

keywords = {annotation, assembly, differential expression analysis, evolution, ncRNAs, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Dukhovny:19,

title = {A CRISPR activation screen identifies genes protecting from Zika virus infection},

author = {Anna Dukhovny and Kevin Lamkiewicz and Qian Chen and Markus Fricke and Nabila Jabrane-Ferrat and Manja Marz and Jae U. Jung and Ella H. Sklan},

doi = {10.1128/JVI.00211-19},

year  = {2019},

date = {2019-07-30},

urldate = {2019-07-30},

journal = {J Virol},

volume = {93},

number = {16},

publisher = {American Society for Microbiology Journals},

abstract = {Zika virus (ZIKV) is an arthropod borne emerging pathogen causing febrile illness. ZIKV is associated Guillain-Barré syndrome and other neurological complications. Infection during pregnancy is associated with pregnancy complications and developmental and neurological abnormalities collectively defined as congenital Zika syndrome. There is still no vaccine or specific treatment for ZIKV infection. To identify host factors that can rescue cells from ZIKV infection we used a genome scale CRISPR activation screen. Our highly ranking hits included a short list of interferon stimulated genes (ISGs) previously reported to have antiviral activity. Validation of the screen results highlighted IFNL2 and IFI6 as genes providing high levels of protection from ZIKV. Activation of these genes had an effect on an early stage in viral infection. In addition, infected cells expressing sgRNAs for both of these genes displayed lower levels of cell death compared to controls. Furthermore, the identified genes were significantly induced in ZIKV infected placenta explants. Thus, these results highlight a set of ISGs directly relevant for rescuing cells from ZIKV infection or its associated cell death and substantiates CRISPR activation screens as a tool to identify host factors impeding pathogen infection.IMPORTANCE Zika virus (ZIKV) is an emerging vector-borne pathogen causing a febrile disease. ZIKV infection might also trigger Guillain-Barré syndrome, neuropathy and myelitis. Vertical transmission of ZIKV can cause fetus demise, still birth or severe congenital abnormalities and neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We used a genome wide CRISPR activation screen, where genes are activated from their native promoters to identify host cell factors that protect cells from ZIKV infection or associated cell death. The results provide better understanding of key host factors that protect cells from ZIKV infection and might assist in identifying novel antiviral targets.},

keywords = {pregnancy, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Peter:19,

title = {Structure and Hierarchy of Influenza Virus Models Revealed by Reaction Network Analysis},

author = {Stephan Peter and Martin Hölzer and Kevin Lamkiewicz and Pietro Speroni Fenizio and Hassan Al Hwaeer and Manja Marz and Stefan Schuster and Peter Dittrich and Bashar Ibrahim},

doi = {10.3390/v11050449},

year  = {2019},

date = {2019-05-16},

urldate = {2019-01-01},

journal = {Viruses},

volume = {11},

number = {5},

pages = {449},

publisher = {MDPI AG},

abstract = {Influenza A virus is recognized today as one of the most challenging viruses that threatens both human and animal health worldwide. Understanding the control mechanisms of influenza infection and dynamics is crucial and could result in effective future treatment strategies. Many kinetic models based on differential equations have been developed in recent decades to capture viral dynamics within a host. These models differ in their complexity in terms of number of species elements and number of reactions. Here, we present a new approach to understanding the overall structure of twelve influenza A virus infection models and their relationship to each other. To this end, we apply chemical organization theory to obtain a hierarchical decomposition of the models into chemical organizations. The decomposition is based on the model structure (reaction rules) but is independent of kinetic details such as rate constants. We found different types of model structures ranging from two to eight organizations. Furthermore, the model’s organizations imply a partial order among models entailing a hierarchy of model, revealing a high model diversity with respect to their long-term behavior. Our methods and results can be helpful in model development and model integration, also beyond the influenza area. },

keywords = {virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Hufsky:19,

title = {The Third Annual Meeting of the European Virus Bioinformatics Center},

author = {Franziska Hufsky and Bashar Ibrahim and Sejal Modha and Martha R. J. Clokie and Stefanie Deinhardt-Emmer and Bas E. Dutilh and Samantha Lycett and Peter Simmonds and Volker Thiel and Aare Abroi and Evelien M. Adriaenssens and Marina Escalera-Zamudio and Jenna Nicole Kelly and Kevin Lamkiewicz and Lu Lu and Julian Susat and Thomas Sicheritz and David L. Robertson and Manja Marz},

doi = {10.3390/v11050420},

year  = {2019},

date = {2019-05-05},

urldate = {2019-05-05},

journal = {Viruses},

volume = {11},

number = {5},

pages = {420},

publisher = {MDPI AG},

abstract = {The Third Annual Meeting of the European Virus Bioinformatics Center (EVBC) took place in Glasgow, United Kingdom, 28–29 March 2019. Virus bioinformatics has become central to virology research, and advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks, being successfully used to detect, control, and treat infections of humans and animals. This active field of research has attracted approximately 110 experts in virology and bioinformatics/computational biology from Europe and other parts of the world to attend the two-day meeting in Glasgow to increase scientific exchange between laboratory- and computer-based researchers. The meeting was held at the McIntyre Building of the University of Glasgow; a perfect location, as it was originally built to be a place for “rubbing your brains with those of other people”, as Rector Stanley Baldwin described it. The goal of the meeting was to provide a meaningful and interactive scientific environment to promote discussion and collaboration and to inspire and suggest new research directions and questions. The meeting featured eight invited and twelve contributed talks, on the four main topics: (1) systems virology, (2) virus-host interactions and the virome, (3) virus classification and evolution and (4) epidemiology, surveillance and evolution. Further, the meeting featured 34 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting. },

keywords = {classification, conference report, evolution, metagenomics, software, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Gerresheim:19,

title = {Cellular Gene Expression during Hepatitis C Virus Replication as Revealed by Ribosome Profiling},

author = {Gesche Gerresheim and Jochen Bathke and Audrey Michel and Dmitri E. Andreev and Lyudmila Shalamova and Oliver Rossbach and Pan Hu and Dieter Glebe and Markus Fricke and Manja Marz and Alexander Goesmann and Stephen Kiniry and Pavel Baranov and Ivan Shatsky and Michael Niepmann},

doi = {10.3390/ijms20061321},

year  = {2019},

date = {2019-03-15},

urldate = {2019-03-15},

journal = {Int J Mol Sci},

volume = {20},

number = {6},

pages = {1321},

publisher = {MDPI AG},

abstract = {Background: Hepatitis C virus (HCV) infects human liver hepatocytes, often leading to liver cirrhosis and hepatocellular carcinoma (HCC). It is believed that chronic infection alters host gene expression and favors HCC development. In particular, HCV replication in Endoplasmic Reticulum (ER) derived membranes induces chronic ER stress. How HCV replication affects host mRNA translation and transcription at a genome wide level is not yet known. Methods: We used Riboseq (Ribosome Profiling) to analyze transcriptome and translatome changes in the Huh-7.5 hepatocarcinoma cell line replicating HCV for 6 days. Results: Established viral replication does not cause global changes in host gene expression—only around 30 genes are significantly differentially expressed. Upregulated genes are related to ER stress and HCV replication, and several regulated genes are known to be involved in HCC development. Some mRNAs (PPP1R15A/GADD34, DDIT3/CHOP, and TRIB3) may be subject to upstream open reading frame (uORF) mediated translation control. Transcriptional downregulation mainly affects mitochondrial respiratory chain complex core subunit genes. Conclusion: After establishing HCV replication, the lack of global changes in cellular gene expression indicates an adaptation to chronic infection, while the downregulation of mitochondrial respiratory chain genes indicates how a virus may further contribute to cancer cell-like metabolic reprogramming (“Warburg effect”) even in the hepatocellular carcinoma cells used here. },

keywords = {cancer, differential expression analysis, liver, RNA structure, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Fuchs:17,

title = {Evolution and Antiviral Specificities of Interferon-Induced Mx Proteins of Bats against Ebola, Influenza, and Other RNA Viruses},

author = {Jonas Fuchs and Martin Hölzer and Mirjam Schilling and Corinna Patzina and Andreas Schoen and Thomas Hoenen and Gert Zimmer and Manja Marz and Friedemann Weber and Marcel A Müller and Georg Kochs},

doi = {10.1128/JVI.00361-17},

year  = {2017},

date = {2017-07-12},

urldate = {2017-07-12},

journal = {J Virol},

volume = {91},

abstract = {Bats serve as a reservoir for various, often zoonotic viruses, including significant human pathogens such as Ebola and influenza viruses. However, for unknown reasons, viral infections rarely cause clinical symptoms in bats. A tight control of viral replication by the host innate immune defense might contribute to this phenomenon. Transcriptomic studies revealed the presence of the interferon-induced antiviral myxovirus resistance (Mx) proteins in bats, but detailed functional aspects have not been assessed. To provide evidence that bat Mx proteins might act as key factors to control viral replication we cloned cDNAs from three bat families, Pteropodidae, Phyllostomidae, and Vespertilionidae. Phylogenetically these bat genes cluster closely with their human ortholog MxA. Using transfected cell cultures, minireplicon systems, virus-like particles, and virus infections, we determined the antiviral potential of the bat Mx1 proteins. Bat Mx1 significantly reduced the polymerase activity of viruses circulating in bats, including Ebola and influenza A-like viruses. The related Thogoto virus, however, which is not known to infect bats, was not inhibited by bat Mx1. Further, we provide evidence for positive selection in bat genes that might explain species-specific antiviral activities of these proteins. Together, our data suggest a role for Mx1 in controlling these viruses in their bat hosts. Bats are a natural reservoir for various viruses that rarely cause clinical symptoms in bats but are dangerous zoonotic pathogens, like Ebola or rabies virus. It has been hypothesized that the interferon system might play a key role in controlling viral replication in bats. We speculate that the interferon-induced Mx proteins might be key antiviral factors of bats and have coevolved with bat-borne viruses. This study evaluated for the first time a large set of bat Mx1 proteins spanning three major bat families for their antiviral potential, including activity against Ebola virus and bat influenza A-like virus, and we describe here their phylogenetic relationship, revealing patterns of positive selection that suggest a coevolution with viral pathogens. By understanding the molecular mechanisms of the innate resistance of bats against viral diseases, we might gain important insights into how to prevent and fight human zoonotic infections caused by bat-borne viruses.},

keywords = {evolution, phylogenetics, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Hoelzer:16,

title = {Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells},

author = {Martin Hölzer and Verena Krähling and Fabian Amman and Emanuel Barth and Stephan H. Bernhart and Victor A. O. Carmelo and Maximilian Collatz and Gero Doose and Florian Eggenhofer and Jan Ewald and Jörg Fallmann and Lasse M. Feldhahn and Markus Fricke and Juliane Gebauer and Andreas J. Gruber and Franziska Hufsky and Henrike Indrischek and Sabina Kanton and Jörg Linde and Nelly F. Mostajo and Roman Ochsenreiter and Konstantin Riege and Lorena Rivarola-Duarte and Abdullah H. Sahyoun and Sita J. Saunders and Stefan E. Seemann and Andrea Tanzer and Bertram Vogel and Stefanie Wehner and Michael T. Wolfinger and Rolf Backofen and Jan Gorodkin and Ivo Grosse and Ivo Hofacker and Steve Hoffmann and Christoph Kaleta and Peter F. Stadler and Stephan Becker and Manja Marz},

doi = {10.1038/srep34589},

year  = {2016},

date = {2016-10-07},

urldate = {2016-10-07},

journal = {Sci Rep},

volume = {6},

pages = {34589},

abstract = {The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.},

keywords = {differential expression analysis, ncRNAs, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Graf:15,

title = {ID: 187: Allelic variations in the interferon-induced human MxA protein affect its antiviral activity against influenza A virus},

author = {Laura Graf and Franziska Sendker and Alexej Dick and Emanuel Barth and Manja Marz and Oliver Daumke and Georg Kochs},

doi = {10.1016/j.cyto.2015.08.192},

year  = {2015},

date = {2015-09-11},

urldate = {2015-09-11},

journal = {Cytokine},

volume = {76},

number = {1},

pages = {98},

publisher = {Elsevier},

abstract = {Human myxovirus resistance protein A (MxA) is an interferon-induced GTPase and part of the host cell defense against influenza viruses. It has a three-domain architecture with an amino-terminal GTPase (G) domain and a carboxy-terminal stalk responsible for oligomerization and viral target recognition. The MX1 gene, encoding MxA, is highly conserved and only a few single nucleotide polymorphisms are described in the human population. In this study we investigate whether and how allelic variations in MxA influence its antiviral function. Two rare nucleotide changes identified in the MX1 gene of healthy individuals result in amino acid exchanges at positions 255 and 268 in the G domain. GTPase and Minireplicon assays revealed that the V268M exchange showed some reduction in GTP hydrolysis, but only a slightly reduced antiviral activity against influenza A virus. However, the G255E exchange caused a complete loss of GTPase and antiviral activity of MxA. Further biochemical analyses of this naturally occurring mutation revealed the central role of GTP binding and hydrolysis for the antiviral mechanism of MxA. Using bioinformatics tools we are currently identifying additional allelic variations in MxA. Their characterization will answer the question how polymorphisms in the MX1 gene influence the antiviral capacity of MxA and whether these are enriched in patients suffering from severe influenza as has been described recently for IFITM3, another interferon-induced antiviral restriction factor.},

keywords = {virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Huang:13,

title = {The duck genome and transcriptome provide insight into an avian influenza virus reservoir species},

author = {Yinhua Huang and Yingrui Li and David W. Burt and Hualan Chen and Yong Zhang and Wubin Qian and Heebal Kim and Shangquan Gan and Yiqiang Zhao and Jianwen Li and Kang Yi and Huapeng Feng and Pengyang Zhu and Bo Li and Qiuyue Liu and Suan Fairley and Katharine E. Magor and Zhenlin Du and Xiaoxiang Hu and Laurie Goodman and Hakim Tafer and Alain Vignal and Taeheon Lee and Kyu-Won Kim and Zheya Sheng and Yang An and Steve Searle and Javier Herrero and Martien A. M. Groenen and Richard P. M. A. Crooijmans and Thomas Faraut and Qingle Cai and Robert G. Webster and Jerry R. Aldridge and Wesley C. Warren and Sebastian Bartschat and Stephanie Kehr and Manja Marz and Peter F. Stadler and Jacqueline Smith and Robert H. S. Kraus and Yaofeng Zhao and Liming Ren and Jing Fei and Mireille Morisson and Pete Kaiser and Darren K. Griffin and Man Rao and Frederique Pitel and Jun Wang and Ning Li},

doi = {10.1038/ng.2657},

year  = {2013},

date = {2013-06-09},

urldate = {2013-06-09},

journal = {Nat Genet},

volume = {45},

pages = {776--783},

abstract = {The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the duck's defense mechanisms against influenza infection have been optimized through the diversification of its β-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses.},

keywords = {DNA / genomics, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Dilcher:12,

title = {Genetic characterization of Tribeč virus and Kemerovo virus, two tick-transmitted human-pathogenic Orbiviruses},

author = {Meik Dilcher and Lekbira Hasib and Marcus Lechner and Nicolas Wieseke and Martin Middendorf and Manja Marz and Andrea Koch and Martin Spiegel and Gerhard Dobler and Frank T Hufert and Manfred Weidmann},

doi = {10.1016/j.virol.2011.11.020},

year  = {2011},

date = {2011-12-20},

urldate = {2011-12-20},

journal = {Virology},

volume = {423},

pages = {68--76},

abstract = {We determined the complete genome sequences of Tribeč virus (TRBV) and Kemerovo virus (KEMV), two tick-transmitted Orbiviruses that can cause diseases of the central nervous system and that are currently classified into the Great Island virus serogroup. VP2 proteins of TRBV and KEMV show very low sequence similarity to the homologous VP4 protein of tick-transmitted Great Island virus (GIV). The new sequence data support previous serological classification of these Orbiviruses into the Kemerovo serogroup, which is different from the Great Island virus serogroup. Genome segment 9 of TRBV and KEMV encodes several overlapping ORF's in the +1 reading frame relative to VP6(Hel). A co-phylogenetic analysis indicates a host switch from insect-borne Orbiviruses toward Ixodes species, which is in disagreement with previously published data.},

keywords = {classification, evolution, insects, phylogenetics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}