Detecting time-resolved and virulence-associated host responses to viral infection

Understanding the cell’s transcriptional response to virus infections is crucial for comprehending the host’s molecular defence, the pathogen’s strategies to circumvent these mechanisms, and hence the viral capability to cause severe disease (i.e. their virulence). However, currently available methods are not sufficient to accurately determine the cellular transcription response, especially for viruses that cause a global host cell shut-off. In these cases, available computational read normalisation strategies prohibit an accurate analysis of differential gene expression. Moreover, current off-the-shelf methods also cannot assess the expression of all relevant transcript classes, in particular the highly repetitive transposable elements (TEs) that have been reported to trigger innate immunity in virus-infected cells. Currently used analysis pipelines do not yet enable the assessment of individual TE copy expression.

Thus, we aim to develop tools for (i) normalisation of reads to accurately measure the host transcription shut-off imposed by viruses and (ii) mapping expression of individual TE copies. Moreover, we aim to (iii) combine these methods into a tool to systematically analyse and cluster expression time series to characterise expression trajectories and infer regulatory interactions during viral infections. We expect that the development and implementation of the proposed software will subsequently enable us to improve the transcriptome-based prediction of a pathogen’s virulence.

Within this project, we will develop and implement methods facilitating the analysis of expression time-series data of the host response for various infection models with varying virulence
  • WP 1: Shut-off-corrected comparison of recurring expression profiles (Weber/Hoffmann)
  • WP 2: Locus-specific expression of endogenous retroviruses in response to viral infection (Hoffmann/Weber)
  • WP 3: Integrative analysis and transcriptome-based virulence prediction (Hoffmann/Weber)

Team Members

Prof. Dr. Steve Hoffmann

Project Leader

Prof. Dr. Friedemann Weber

Project Leader

N. N.

Doctoral Researcher

N. N.

Doctoral Researcher

Besim Berisha

Associated Technician

Silke Förste

Associated Lab Manager

Project-Specific Publications

2025

Wiechens, Elina; Vigliotti, Flavia; Siniuk, Kanstantsin; Schwarz, Robert; Schwab, Katjana; Riege, Konstantin; Bömmel, Alena; Görlich, Ivonne; Bens, Martin; Sahm, Arne; Groth, Marco; Sammons, Morgan A; Loewer, Alexander; Hoffmann, Steve; Fischer, Martin

Gene regulation by convergent promoters Journal Article

In: Nat Genet, vol. 57, iss. 1, no. 1, pp. 206-217, 2025.

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2024

Hofmann, Nina; Bartkuhn, Marek; Becker, Stephan; Biedenkopf, Nadine; Böttcher-Friebertshäuser, Eva; Brinkrolf, Karina; Dietzel, Erik; Fehling, Sarah Katharina; Goesmann, Alexander; Heindl, Miriam Ruth; Hoffmann, Simone; Karl, Nadja; Maisner, Andrea; Mostafa, Ahmed; Kornecki, Laura; Müller-Kräuter, Helena; Müller-Ruttloff, Christin; Nist, Andrea; Pleschka, Stephan; Sauerhering, Lucie; Stiewe, Thorsten; Strecker, Thomas; Wilhelm, Jochen; Wuerth, Jennifer D.; Ziebuhr, John; Weber, Friedemann; Schmitz, M. Lienhard

Distinct negative-sense RNA viruses induce a common set of transcripts encoding proteins forming an extensive network. Journal Article

In: J Virol, vol. 98, iss. 10, no. 10, pp. e0093524, 2024.

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Olecka, Maja; Bömmel, Alena; Best, Lena; Haase, Madlen; Foerste, Silke; Riege, Konstantin; Dost, Thomas; Flor, Stefano; Witte, Otto W; Franzenburg, Sören; Groth, Marco; Eyss, Björn; Kaleta, Christoph; Frahm, Christiane; Hoffmann, Steve

Nonlinear DNA methylation trajectories in aging male mice Journal Article

In: Nat Commun, vol. 15, iss. 1, no. 1, pp. 3074, 2024, ISSN: 2041-1723 (Electronic) 2041-1723 (Linking).

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2022

Schwarz, Robert; Koch, Philipp; Wilbrandt, Jeanne; Hoffmann, Steve

Locus-specific expression analysis of transposable elements. Journal Article

In: Brief Bioinform, vol. 23, iss. 1, 2022, ISSN: 1477-4054.

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2020

Schoen, Andreas; Lau, Simone; Verbruggen, Paul; Weber, Friedemann

Elongin C contributes to RNA polymerase II degradation by the interferon antagonist NSs of La Crosse Orthobunyavirus Journal Article

In: J Virol, vol. 94, iss. 7, 2020.

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2019

Hölzer, Martin; Schoen, Andreas; Wulle, Julia; Müller, Marcel A; Drosten, Christian; Marz, Manja; Weber, Friedemann

Virus- and interferon alpha-induced transcriptomes of cells from the microbat emphMyotis daubentonii Journal Article

In: iScience, vol. 19, pp. 647-661, 2019, ISSN: 2589-0042.

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2018

Wuerth, Jennifer Deborah; Habjan, Matthias; Wulle, Julia; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann

NSs protein of sandfly fever Sicilian phlebovirus counteracts interferon (IFN) induction by masking the DNA-binding domain of IFN regulatory factor 3 Journal Article

In: J Virol, vol. 92, iss. 23, 2018.

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2014

Hoffmann, Steve; Otto, Christian; Doose, Gero; Tanzer, Andrea; Langenberger, David; Christ, Sabina; Kunz, Manfred; Holdt, Lesca M; Teupser, Daniel; Hackermüller, Jörg; Stadler, Peter F

A multi-split mapping algorithm for circular RNA, splicing, trans-splicing and fusion detection. Journal Article

In: Genome Biol, vol. 15, iss. 2, pp. R34, 2014, ISSN: 1474-760X.

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Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann

Virulence factor NSs of Rift Valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH Journal Article

In: J Virol, vol. 88, no. 6, pp. 3464-3473, 2014.

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2009

Hoffmann, Steve; Otto, Christian; Kurtz, Stefan; Sharma, Cynthia M; Khaitovich, Philipp; Vogel, Jörg; Stadler, Peter F; Hackermüller, Jörg

Fast mapping of short sequences with mismatches, insertions and deletions using index structures. Journal Article

In: PLoS Comput Biol, vol. 5, iss. 9, pp. e1000502, 2009, ISSN: 1553-7358.

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