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2. Reston and Zaire Ebolavirus Life cycle and host cellular response: a comparative study

Author

Mostajo, Nelly

Subjects
Zelllinie, Transkriptom, Viren, Ebola-Virus, Lebensdauer
Abstract

Ebolaviruses are negative strand RNA viruses which are known to cause Ebola virus disease (EVD) with a fatal outcome in primates. All five species of Ebolavirus can infect humans, but only four lead to EVD. The Ebolavirus with the most provoked outbreaks and highest fatality rate (above 80%) is Zaire ebolavirus (EBOV), while the one without any provoke symptoms in humans is Reston ebolavirus (RESTV). In order to determine the features which lead to the different outcomes from EBOV and RESTV the cellular response against these viruses, and the divergence between RESTV and EBOV life cycle inside human cells was investigated. To study the cellular response RNA of two human cell lines (HuH7 and THP1) infected with RESTV, EBOV and uninfected (Mock) at two different time points was analyzed. Using whole transcriptome screening with smallRNAseq, Microarray, de novo annotation and expression profiles it was possible to elucidate that the cellular response against RESTV and EBOV infection differs the most at 3 h p.i., this was consistent in HuH7 and THP1 cell lines. The transcriptomic study showed RESTV and EBOV stimulate a distinct set of genes related to cellular entry. Also, the transcriptomic data suggests EBOV transcribes and replicates faster than RESTV, supported by cellular components like snoRNAs, while RESTV is similar to Mock in this aspect. This finding was backed with an entry assay which showed EBOV releases its content into the cytosol faster than RESTV, pointing to differences in entry pathway or a better time controlled response from the cell against RESTV. To understand the life cycle of RESTV and EBOV in human cells transcription/replication, inclusion bodies, nucleocapsid (NC) transport, viral particle formation, and infection was studied. Selected genes which were differentially expressed between RESTV and EBOV infected cells were further analyzed on the virus life cycle context.

Published
2020
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4. Massive Effect on LncRNAs in Human Monocytes During Fungal and Bacterial Infections and in Response to Vitamins A and D

Author

Riege, Konstantin, primary, Hölzer, Martin, additional, Klassert, Tilman E., additional, Barth, Emanuel, additional, Bräuer, Julia, additional, Collatz, Maximilian, additional, Hufsky, Franziska, additional, Mostajo, Nelly, additional, Stock, Magdalena, additional, Vogel, Bertram, additional, Slevogt, Hortense, additional, and Marz, Manja, additional

Published
2017
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5. Correction: Corrigendum: Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells

Author

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

Published
2017
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6. Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells:[Plus] Corrigendum

Author

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

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.

Published
2016

7. Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells

Author

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

Published
2016
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9. Genome-Wide Identification and Mapping of NBSEncoding Resistance Genes in Solanum tuberosum Group Phureja.

Author

Lozano, Roberto, Ponce, Olga, Ramirez, Manuel, Mostajo, Nelly, and Orjeda, Gisella

Subjects
POTATO diseases & pests, NATURAL immunity, GENE mapping, GENETIC code, PLANT diseases
Abstract

The majority of disease resistance (R) genes identified to date in plants encode a nucleotide-binding site (NBS) and leucinerich repeat (LRR) domain containing protein. Additional domains such as coiled-coil (CC) and TOLL/interleukin-1 receptor (TIR) domains can also be present. In the recently sequenced Solanum tuberosum group phureja genome we used HMM models and manual curation to annotate 435 NBS-encoding R gene homologs and 142 NBS-derived genes that lack the NBS domain. Highly similar homologs for most previously documented Solanaceae R genes were identified. A surprising ∼41% (179) of the 435 NBS-encoding genes are pseudogenes primarily caused by premature stop codons or frameshift mutations. Alignment of 81.80% of the 577 homologs to S. tuberosum group phureja pseudomolecules revealed non-random distribution of the R-genes; 362 of 470 genes were found in high density clusters on 11 chromosomes. [ABSTRACT FROM AUTHOR]

Published
2012
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10. A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes.

Author

Mostajo NF, Lataretu M, Krautwurst S, Mock F, Desirò D, Lamkiewicz K, Collatz M, Schoen A, Weber F, Marz M, and Hölzer M

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Published
2020
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11. Corrigendum: Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells.

Author

Hölzer M, Krähling V, Amman F, Barth E, Bernhart SH, Carmelo VA, Collatz M, Doose G, Eggenhofer F, Ewald J, Fallmann J, Feldhahn LM, Fricke M, Gebauer J, Gruber AJ, Hufsky F, Indrischek H, Kanton S, Linde J, Mostajo N, Ochsenreiter R, Riege K, Rivarola-Duarte L, Sahyoun AH, Saunders SJ, Seemann SE, Tanzer A, Vogel B, Wehner S, Wolfinger MT, Backofen R, Gorodkin J, Grosse I, Hofacker I, Hoffmann S, Kaleta C, Stadler PF, Becker S, and Marz M

Published
2017
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