
Viruses circulate predominantly in their natural reservoir host but frequently also infect other species. However, to establish a new lineage the virus has to adapt to the new environment by acquiring advantageous new mutations. These mutations also influence the secondary structure of the viral DNA and RNA, in turn affecting the replication process. ESR 8 will study the fundamental correlation between virus evolution and RNA secondary structures.
Being more specific, in case of segmented genomes (e.g. influenza A virus (IAV)) packaging is influenced by the secondary structure of the virus genomic RNA segments. In cells co-infected with different viruses, new variants with mixed genomes can emerge that have the potential to overcome the natural host species barrier and to cause a devastating pandemic. Mixing of viral segments, also designated genetic reassortment, is possible due to very efficient incorporation of different genome segments into one virus particle.
ESR 2 will systematically generate reassortant viruses between two human IAVs and select those that replicate most efficiently for further functional studies. Additionally, ESR 2 will use chemical probing to compare the genome structure in parental and those reassortant viruses. ESR 1 will study genetic reassortment events of IAV and especially the role of RNA-RNA interaction that is supposed to coordinate the interaction of the different genomes which are finally incorporated into viral particles. The focus of ESR 1 is to develop a computational tool that can predict the complex interplay of the RNA-RNA interaction required for genome packing between quite diverse IAV based on experimental data.
PhD Projects
- ESR 1: Deciphering the RNA genome packaging code of influenza A viruses
- ESR 2: Mechanism of coordinated incorporation of segmented virus genomes into viral particles
Journal Articles
Hufsky, Franziska; Abecasis, Ana B.; Babaian, Artem; Beck, Sebastian; Brierley, Liam; Dellicour, Simon; Eggeling, Christian; Elena, Santiago F.; Gieraths, Udo; Ha, Anh D.; Harvey, Will; Jones, Terry C.; Lamkiewicz, Kevin; Lovate, Gabriel Lencioni; Lücking, Dominik; Machyna, Martin; Nishimura, Luca; Nocke, Maximilian K.; Renard, Bernard Y.; Sakaguchi, Shoichi; Sakellaridi, Lygeri; Spangenberg, Jannes; Tarradas-Alemany, Maria; Triebel, Sandra; Vakulenko, Yulia; Wijesekara, Yasas; González-Candelas, Fernando; Krautwurst, Sarah; Pérez-Cataluña, Alba; Randazzo, Walter; Sánchez, Gloria; Marz, Manja
The International Virus Bioinformatics Meeting 2023. Journal Article
In: Viruses, vol. 15, iss. 10, pp. 2031, 2023.
@article{nokey,
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 Lencioni 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 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},
year = {2023},
date = {2023-09-30},
urldate = {2023-09-30},
journal = {Viruses},
volume = {15},
issue = {10},
pages = {2031},
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 = {},
pubstate = {published},
tppubtype = {article}
}
Jakob, Celia; Lovate, Gabriel Lencioni; Desirò, Daniel; Gießler, Lara; Smyth, Redmond P.; Marquet, Roland; Lamkiewicz, Kevin; Marz, Manja; Schwemmle, Martin; Bolte, Hardin
Sequential disruption of SPLASH-identified vRNA–vRNA interactions challenges their role in influenza A virus genome packaging Journal Article
In: Nucleic Acids Research, vol. 51, iss. 12, pp. 6479-6494, 2023.
@article{,
title = {Sequential disruption of SPLASH-identified vRNA–vRNA interactions challenges their role in influenza A virus genome packaging},
author = {Celia Jakob and Gabriel Lencioni Lovate and Daniel Desirò and Lara Gießler and Redmond P. Smyth and Roland Marquet and Kevin Lamkiewicz and Manja Marz and Martin Schwemmle and Hardin Bolte},
doi = {doi:10.1093/nar/gkad442},
year = {2023},
date = {2023-05-24},
urldate = {2023-05-24},
journal = {Nucleic Acids Research},
volume = {51},
issue = {12},
pages = {6479-6494},
abstract = {A fundamental step in the influenza A virus (IAV) replication cycle is the coordinated packaging of eight distinct genomic RNA segments (i.e. vRNAs) into a viral particle. Although this process is thought to be controlled by specific vRNA–vRNA interactions between the genome segments, few functional interactions have been validated. Recently, a large number of potentially functional vRNA–vRNA interactions have been detected in purified virions using the RNA interactome capture method SPLASH. However, their functional significance in coordinated genome packaging remains largely unclear. Here, we show by systematic mutational analysis that mutant A/SC35M (H7N7) viruses lacking several prominent SPLASH-identified vRNA–vRNA interactions involving the HA segment package the eight genome segments as efficiently as the wild-type virus. We therefore propose that the vRNA–vRNA interactions identified by SPLASH in IAV particles are not necessarily critical for the genome packaging process, leaving the underlying molecular mechanism elusive.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Jakob, Celia; Paul-Stansilaus, Rithu; Schwemmle, Martin; Marquet, Roland; Bolte, Hardin
The influenza A virus genome packaging network - complex, flexible and yet unsolved Journal Article
In: Nucleic Acids Res., 2022.
@article{nokey,
title = {The influenza A virus genome packaging network - complex, flexible and yet unsolved},
author = {Celia Jakob and Rithu Paul-Stansilaus and Martin Schwemmle and Roland Marquet and Hardin Bolte},
doi = {10.1093/nar/gkac688},
year = {2022},
date = {2022-08-22},
journal = {Nucleic Acids Res.},
abstract = {The genome of influenza A virus (IAV) consists of eight unique viral RNA segments. This genome organization allows genetic reassortment between co-infecting IAV strains, whereby new IAVs with altered genome segment compositions emerge. While it is known that reassortment events can create pandemic IAVs, it remains impossible to anticipate reassortment outcomes with pandemic prospects. Recent research indicates that reassortment is promoted by a viral genome packaging mechanism that delivers the eight genome segments as a supramolecular complex into the virus particle. This finding holds promise of predicting pandemic IAVs by understanding the intermolecular interactions governing this genome packaging mechanism. Here, we critically review the prevailing mechanistic model postulating that IAV genome packaging is orchestrated by a network of intersegmental RNA-RNA interactions. Although we find supporting evidence, including segment-specific packaging signals and experimentally proposed RNA-RNA interaction networks, this mechanistic model remains debatable due to a current shortage of functionally validated intersegmental RNA-RNA interactions. We speculate that identifying such functional intersegmental RNA-RNA contacts might be hampered by limitations of the utilized probing techniques and the inherent complexity of the genome packaging mechanism. Nevertheless, we anticipate that improved probing strategies combined with a mutagenesis-based validation could facilitate their discovery.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hufsky, Franziska; Beslic, Denis; Boeckaerts, Dimitri; Duchene, Sebastian; González-Tortuero, Enrique; Gruber, Andreas J.; Guo, Jiarong; Jansen, Daan; Juma, John; Kongkitimanon, Kunaphas; Luque, Antoni; Ritsch, Muriel; Lovate, Gabriel Lencioni; Nishimura, Luca; Pas, Célia; Domingo, Esteban; Hodcroft, Emma; Lemey, Philippe; Sullivan, Matthew B.; Weber, Friedemann; González-Candelas, Fernando; Krautwurst, Sarah; Pérez-Cataluña, Alba; Randazzo, Walter; Sánchez, Gloria; Marz, Manja
The International Virus Bioinformatics Meeting 2022 Journal Article
In: Viruses, vol. 14, iss. 5, pp. 973, 2022.
@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 Lencioni 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 = {},
pubstate = {published},
tppubtype = {article}
}
Goettsch, Winfried; Beerenwinkel, Niko; Deng, Li; Dölken, Lars; Dutilh, Bas E.; Erhard, Florian; Kaderali, Lars; von Kleist, Max; Marquet, Roland; Matthijnssens, Jelle; McCallin, Shawna; McMahon, Dino; Rattei, Thomas; van Rij, Ronald P.; Robertson, David L.; Schwemmle, Martin; Stern-Ginossar, Noam; Marz, Manja
ITN -- VIROINF: Understanding (Harmful) Virus-Host Interactions by Linking Virology and Bioinformatics Journal Article
In: Viruses, vol. 13, no. 5, pp. 766, 2021.
@article{nokey,
title = {ITN -- VIROINF: Understanding (Harmful) Virus-Host Interactions by Linking Virology and Bioinformatics},
author = {Winfried Goettsch and Niko Beerenwinkel and Li Deng and Lars Dölken and Bas E. Dutilh and Florian Erhard and Lars Kaderali and Max von 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},
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 = {},
pubstate = {published},
tppubtype = {article}
}
Presentations
Lovate, Gabriel Lencioni
Using high-throughput analysis to understand RNA-RNA interactions of Influenza Presentation
Talk at DiagnosTech Lecture, 29.04.2022.
@misc{nokey,
title = {Using high-throughput analysis to understand RNA-RNA interactions of Influenza},
author = {Gabriel Lencioni Lovate},
url = {https://www.infectognostics.de/termine/rnaswarm},
year = {2022},
date = {2022-04-29},
urldate = {2022-04-29},
abstract = {As a segmented RNA virus, Influenza is a frequently changing its genome. Each year, this leads to pandemic strains and continuous efforts to adapt vaccines to newly emerging antigens of Influenza. To improve the understanding of this antigenic diversity, researchers from the European Virus Bioinformatics Center (EVBC) are analysing the specific RNA-RNA interactions that play an essential role in the packaging and the corresponding selective reassortment of Influenza (A) genomes.
In this lecture, EVBC scientist Gabriel Lencioni Lovate will present "RNAswarm", a new software pipeline that is expanding the scope of high-throughput analyses of RNA-RNA interactions. In particular, RNAswarm allows for statistically comparing the frequency of RNA interactions among different strains or experimental settings. Thus, RNAswarm offers virologists an automated and consistent method for prioritising and comparing the RNA-RNA interactions, a time-consuming job prone to individual biases when performed manually.},
howpublished = {Talk at DiagnosTech Lecture},
keywords = {},
pubstate = {published},
tppubtype = {presentation}
}
In this lecture, EVBC scientist Gabriel Lencioni Lovate will present "RNAswarm", a new software pipeline that is expanding the scope of high-throughput analyses of RNA-RNA interactions. In particular, RNAswarm allows for statistically comparing the frequency of RNA interactions among different strains or experimental settings. Thus, RNAswarm offers virologists an automated and consistent method for prioritising and comparing the RNA-RNA interactions, a time-consuming job prone to individual biases when performed manually.
Paul-Stansilaus, Rithu
Identification of RNA-RNA interactions that drive genetic reassortment between human H1N1 and H3N2 viruses Presentation
Oral presentation at 3rd ResaFlu meeting 2022, 13.04.2022.
@misc{nokey,
title = {Identification of RNA-RNA interactions that drive genetic reassortment between human H1N1 and H3N2 viruses},
author = {Rithu Paul-Stansilaus},
year = {2022},
date = {2022-04-13},
howpublished = {Oral presentation at 3rd ResaFlu meeting 2022},
keywords = {},
pubstate = {published},
tppubtype = {presentation}
}
Paul-Stansilaus, Rithu
Identification of RNA-RNA interactions that drive genetic reassortment between human H1N1 and H3N2 viruses Presentation
Poster at XXIVemes Journées Francophones de Virologie 2022, 11.04.2022.
@misc{nokey,
title = {Identification of RNA-RNA interactions that drive genetic reassortment between human H1N1 and H3N2 viruses},
author = {Rithu Paul-Stansilaus},
year = {2022},
date = {2022-04-11},
howpublished = {Poster at XXIVemes Journées Francophones de Virologie 2022},
keywords = {},
pubstate = {published},
tppubtype = {presentation}
}
Lovate, Gabriel Lencioni
RNAswarm: A pipeline for differential RNA-RNA Interaction probing Presentation
Oral poster at 31st Annual Meeting of the Society for Virology 2022, Munich, Germany, 30.03.2022.
@misc{nokey,
title = {RNAswarm: A pipeline for differential RNA-RNA Interaction probing},
author = {Gabriel Lencioni Lovate},
year = {2022},
date = {2022-03-30},
urldate = {2022-03-30},
howpublished = {Oral poster at 31st Annual Meeting of the Society for Virology 2022, Munich, Germany},
keywords = {},
pubstate = {published},
tppubtype = {presentation}
}
Lovate, Gabriel Lencioni
Reproducible RNA-RNA interaction probing for RNA proximity ligation data with RNAswarm Presentation
Poster at International Virus Bioinformatics Meeting 2022, 24.03.2022, (Best Poster Award).
@misc{nokey,
title = {Reproducible RNA-RNA interaction probing for RNA proximity ligation data with RNAswarm},
author = {Gabriel Lencioni Lovate},
url = {https://evbc.uni-jena.de/events/vibiom2022/},
year = {2022},
date = {2022-03-24},
howpublished = {Poster at International Virus Bioinformatics Meeting 2022},
note = {Best Poster Award},
keywords = {},
pubstate = {published},
tppubtype = {presentation}
}