@article{pmid42135491,

title = {Sequence to structure insights into Lassa virus population-level biophysical properties and glycoprotein structure catalogue},

author = {Richard Olumide Daodu and Jakob R Riccabona and Antonia Sophia Peter and Jens-Uwe Ulrich and Isabel von Creytz and Joseph B Prescott and Knut Reinert and Clara T Schoeder and Denise Kühnert},

doi = {10.1038/s44298-026-00196-3},

issn = {2948-1767},

year  = {2026},

date = {2026-05-01},

urldate = {2026-05-01},

journal = {Npj Viruses},

volume = {4},

number = {1},

abstract = {Lassa virus (LASV) remains a major public health threat in West Africa, with recurrent outbreaks, exported cases, and no licensed vaccine. LASV lineages are geographically separated and differ in immunogenicity and pathogenicity; however, the fundamental biophysical properties that may explain these differences remain poorly defined. Here, we analyse LASV protein properties at the population scale across lineages, focusing on the glycoprotein (GP), the principal target of humoral immunity. Across hundreds of curated sequences, protein length variation is driven primarily by short indels, with pronounced variation in the RNA polymerase and a recurrent one-amino-acid difference in GP. In parallel, population-scale analyses reveal subtle lineage- and protein-specific differences in amino-acid composition across the LASV proteins. Despite co-circulation in Nigeria, S-segment-encoded proteins from lineage III are consistently heavier than those from lineage II. An integrative framework combining random forest feature importance, Manhattan-distance profiling, Pearson correlation, and amino-acid composition analyses reveals that lineage III GPs are ~180 Da heavier on average, driven by shifts toward the use of heavier residues at specific sites. Population-scale computational structural modelling and flow-cytometric assays indicate that the N-terminal GP1 indel is structurally and functionally tolerated. Together, these findings define lineage-specific biophysical patterns in LASV and provide a catalogue of GP structures to inform vaccine and therapeutic design.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41511982,

title = {Exonuclease ISG20 inhibits human cytomegalovirus replication by inducing an innate immune defense signature},

author = {Matthias Hehl and Myriam Scherer and Cora Stegmann and Eva-Maria Raubuch and Claudia Ploil and Teresa Rummel and Philipp Kirchner and Nina Kottmann and Anna Reichel and Anna Katharina Kuderna and Anne-Charlotte König and Caroline C Friedel and Florian Erhard and Thomas Stamminger},

doi = {10.1371/journal.ppat.1013856},

issn = {1553-7374},

year  = {2026},

date = {2026-01-01},

urldate = {2026-01-01},

journal = {PLoS Pathog},

volume = {22},

number = {1},

pages = {e1013856},

abstract = {ISG20 is an interferon-regulated protein that exhibits RNase activity thereby inhibiting the replication of a broad spectrum of RNA viruses. By single cell RNA sequencing, we identified ISG20 as an antiviral factor for human cytomegalovirus (HCMV) as it was upregulated in a population of HCMV-resistant cells. In accordance with an antiviral role on herpesviruses, overexpression of ISG20 in primary human fibroblasts led to reduced HCMV and HSV-1 replication, while knockdown of ISG20 enhanced virus growth. In Western blot kinetics, we observed that inhibition of HCMV replication by ISG20 occurs at the early stage of infection which correlated with reduced amounts of viral early and late transcripts. However, neither the half-life of viral and cellular RNAs nor of viral DNA was decreased in ISG20-expressing cells, indicating that ISG20 does not exert its antiviral effect via a degradation of RNAs or DNA. Instead, RNA-seq analysis revealed an innate immune defense signature upon ISG20 expression that comprised the upregulation of a distinct set of interferon stimulated genes (ISGs), zinc finger protein genes (ZNFs) and of transposable elements (TEs). Our data indicate that this gene signature augments both IFN production and response of the host cell. Consistently, the JAK-STAT inhibitor ruxolitinib rescued HCMV gene expression in ISG20-expressing cells. We conclude that ISG20 induces a broad immune defense signature that serves to amplify the IFN-mediated host cell defense thus explaining its extended antiviral activity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Daodu:25,

title = {CLASV: Rapid Lassa virus lineage assignment with random forest.},

author = {Richard Olumide Daodu and Ebenezer Awotoro and Jens-Uwe Ulrich and Denise Kühnert},

url = {https://pubmed.ncbi.nlm.nih.gov/40924753/},

doi = {10.1371/journal.pntd.0013512},

issn = {1935-2735},

year  = {2025},

date = {2025-09-01},

journal = {PLoS Negl Trop Dis},

volume = {19},

issue = {9},

pages = {e0013512},

keywords = {},

pubstate = {epublish},

tppubtype = {article}

}

@article{pmid42004175,

title = {Identification of Viral Variants from Functional Genomics Data},

author = {Florian Röckl and Caroline C Friedel},

doi = {10.12688/f1000research.168786.2},

issn = {2046-1402},

year  = {2025},

date = {2025-01-01},

urldate = {2025-01-01},

journal = {F1000Res},

volume = {14},

pages = {794},

abstract = {BACKGROUND: Virus mutants are commonly used for studying the role of individual viral proteins in infections and are increasingly investigated with functional genomics experiments of infected cells that use sequencing-based assays such as RNA-seq or ATAC-seq. However, existing mutant virus strains are often poorly documented, in particular if they have been created decades ago. Identifying viral variants directly in the functional genomics experiments avoids additional genome sequencing and allows confirming the presence of specific mutations directly in the experiment of interest.nnMETHODS: We present a pipeline to directly identify mutations in viral genomes from sequencing-based functional genomics data. The pipeline combines existing SNP callers with novel methods for identifying deletions, insertions, and corresponding inserted sequences. These novel methods address the problem that existing structural variant callers performed poorly on functional genomics data with large variations in read coverage.nnRESULTS: We evaluated the pipeline on RNA-seq data for infection with knockout mutants for important proteins of Herpes simplex virus 1 (HSV-1). Comparison of the variants identified by our pipeline with the descriptions of the original publications showed that we could correctly recover the introduced mutations.nnCONCLUSIONS: Our pipeline offers researchers a fast and easy way to identify variants in the viral genome without additional genome sequencing. The pipeline is implemented as a workflow for the workflow management system Watchdog and is available at https://github.com/watchdog-wms/watchdog-wms-workflows/ (workflow VariantCallerPipeline).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Esquivel:24,

title = {Recombination-aware phylogenetic analysis sheds light on the evolutionary origin of SARS-CoV-2.},

author = {Luis Roger Esquivel Gomez and Ariane Weber and Arthur Kocher and Denise Kühnert},

url = {https://pubmed.ncbi.nlm.nih.gov/38177346/},

doi = {10.1038/s41598-023-50952-1},

issn = {2045-2322},

year  = {2024},

date = {2024-01-01},

journal = {Sci. Rep.},

volume = {14},

issue = {1},

pages = {541},

keywords = {},

pubstate = {epublish},

tppubtype = {article}

}

@article{Djakovic:23,

title = {The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes.},

author = {Lara Djakovic and Thomas Hennig and Katharina Reinisch and Andrea Milić and Adam W Whisnant and Katharina Wolf and Elena Weiß and Tobias Haas and Arnhild Grothey and Christopher S Jürges and Michael Kluge and Elmar Wolf and Florian Erhard and Caroline C Friedel and Lars Dölken},

doi = {10.1038/s41467-023-40217-w},

issn = {2041-1723},

year  = {2023},

date = {2023-01-01},

journal = {Nat Commun},

volume = {14},

number = {1},

issue = {1},

pages = {4591},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Smith:21,

title = {Rapid incidence estimation from SARS-CoV-2 genomes reveals decreased case detection in Europe during summer 2020.},

author = {Maureen Rebecca Smith and Maria Trofimova and Ariane Weber and Yannick Duport and Denise Kühnert and Max Kleist},

doi = {10.1038/s41467-021-26267-y},

issn = {2041-1723},

year  = {2021},

date = {2021-01-01},

journal = {Nat Commun},

volume = {12},

number = {1},

issue = {1},

pages = {6009},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kocher:21,

title = {Ten millennia of hepatitis B virus evolution.},

author = {Arthur Kocher and Luka Papac and Rodrigo Barquera and Felix M Key and Maria A Spyrou and Ron Hübler and Adam B Rohrlach and Franziska Aron and Raphaela Stahl and Antje Wissgott and Florian Bömmel and Maria Pfefferkorn and Alissa Mittnik and Vanessa Villalba-Mouco and Svend Hansen and Egor P Kitov and Miroslav Dobeš and Michal Ernée and Harald Meller and Kurt W Alt and Kay Prüfer and Christina Warinner and Stephan Schiffels and Philipp W Stockhammer and Kirsten Bos and Cosimo Posth and Alexander Herbig and Wolfgang Haak and Johannes Krause and Denise Kühnert},

doi = {10.1126/science.abi5658},

issn = {1095-9203},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Science},

volume = {374},

number = {6564},

issue = {6564},

pages = {182–188},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Whisnant:20,

title = {Integrative functional genomics decodes herpes simplex virus 1},

author = {Adam W Whisnant and Christopher S Jürges and Thomas Hennig and Emanuel Wyler and Bhupesh Prusty and Andrzej J Rutkowski and Anne L'hernault and Lara Djakovic and Margarete Göbel and Kristina Döring and Jennifer Menegatti and Robin Antrobus and Nicholas J Matheson and Florian W H Künzig and Guido Mastrobuoni and Chris Bielow and Stefan Kempa and Chunguang Liang and Thomas Dandekar and Ralf Zimmer and Markus Landthaler and Friedrich Grässer and Paul J Lehner and Caroline C Friedel and Florian Erhard and Lars Dölken},

doi = {10.1038/s41467-020-15992-5},

year  = {2020},

date = {2020-01-01},

journal = {Nat Commun},

volume = {11},

issue = {1},

pages = {2038},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kuehnert:18,

title = {Quantifying the fitness cost of HIV-1 drug resistance mutations through phylodynamics.},

author = {Denise Kühnert and Roger Kouyos and George Shirreff and Jūlija Pečerska and Alexandra U Scherrer and Jürg Böni and Sabine Yerly and Thomas Klimkait and Vincent Aubert and Huldrych F Günthard and Tanja Stadler and Sebastian Bonhoeffer and Swiss HIV Cohort Study},

doi = {10.1371/journal.ppat.1006895},

issn = {1553-7374},

year  = {2018},

date = {2018-01-01},

journal = {PLoS Pathog},

volume = {14},

number = {2},

issue = {2},

pages = {e1006895},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hennig:18,

title = {HSV-1-induced disruption of transcription termination resembles a cellular stress response but selectively increases chromatin accessibility downstream of genes.},

author = {Thomas Hennig and Marco Michalski and Andrzej J Rutkowski and Lara Djakovic and Adam W Whisnant and Marie-Sophie Friedl and Bhaskar Anand Jha and Marisa A P Baptista and Anne L'Hernault and Florian Erhard and Lars Dölken and Caroline C Friedel},

doi = {10.1371/journal.ppat.1006954},

issn = {1553-7374},

year  = {2018},

date = {2018-01-01},

journal = {PLoS Pathog},

volume = {14},

number = {3},

issue = {3},

pages = {e1006954},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bonfert:17,

title = {Prediction of poly(A) sites by poly(A) read mapping.},

author = {Thomas Bonfert and Caroline C Friedel},

url = {https://pubmed.ncbi.nlm.nih.gov/28135292/},

doi = {10.1371/journal.pone.0170914},

issn = {1932-6203},

year  = {2017},

date = {2017-01-01},

journal = {PLoS One},

volume = {12},

number = {1},

issue = {1},

pages = {e0170914},

keywords = {},

pubstate = {epublish},

tppubtype = {article}

}

@article{Rutkowski:15,

title = {Widespread disruption of host transcription termination in HSV-1 infection.},

author = {Andrzej J Rutkowski and Florian Erhard and Anne L'Hernault and Thomas Bonfert and Markus Schilhabel and Colin Crump and Philip Rosenstiel and Stacey Efstathiou and Ralf Zimmer and Caroline C Friedel and Lars Dölken},

doi = {10.1038/ncomms8126},

issn = {2041-1723},

year  = {2015},

date = {2015-01-01},

journal = {Nat Commun},

volume = {6},

pages = {7126},

keywords = {},

pubstate = {published},

tppubtype = {article}

}