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Characterizing host factors as targets to develop broadly acting therapeutics against emerging viruses
Summary
Most virus infections - especially those caused by emerging viruses - still lack effective treatments. One promising strategy is to target virus-host interactions that are shared by many different viruses. These interactions are essential for viruses to replicate inside the body and could be used to develop broad-spectrum antiviral therapies, including treatments for future unknown threats like "Disease X."
To explore this approach, researchers performed a large-scale screen to find human proteins that Ebola virus (EBOV) and Junín virus (JUNV) depend on to complete their life cycle. Despite their genetic differences, both viruses share key features in how they interact with human cells. Several host proteins were identified as essential for both viruses.
The project now focuses on understanding how these shared host factors - such as RBM15, ZC3H13, ABDH16A, and PRSS23 - support virus infection. The team will study how these proteins interact with viral components and test existing drugs that could block these interactions. With support from other CRC groups, the goal is to expand this work to additional emerging viruses and pave the way for the development of broadly acting antiviral therapies.
Our Work Packages (WP):
WP1: Analysis of the functional role of the identified host factors in the filovirus and arenavirus life cycles.
WP2: Characterization of the interaction of the identified host factors with viral factors to define molecular targets for broadly active therapeutics.
WP3: Targeting the identified host factors to impair filovirus and arenavirus infection.
The working packages aim to identify and characterize key host cell factors involved in the life cycle of emerging viruses, providing a foundation for the development and testing of broad-spectrum, host-directed antivirals with potential effectiveness against high-consequence pathogens, including “Disease X.”
Team
Dr. Allison Groseth
Principal Investigator
E-mail address:
Phone: + 49 38351 7-1101
Dr. Thomas Hoenen
Principal Investigator
E-mail address:
Phone: +49 38351 7-1028
Research Group Groseth
The Laboratory for Arenavirus Biology is based at the Friedrich-Loeffler-Institut (FLI) on the Isle of Riems.
Research Group Hoenen
The Laboratory for Integrative Cell and Infection Biology is based at the Friedrich-Loeffler-Institut (FLI) on the Isle of Riems.
Project related publications
Bodmer BS, Wendt L, Dupré J, Groseth A, Hoenen T. Antiviral defense against filovirus infections: targets and evasion mechanisms. Future Microbiol. 2025 May 7:1–15. doi: 10.1080/17460913.2025.2501924. Epub ahead of print. PMID: 40331244.
Bodmer BS, Vallbracht M, Ushakov DS, Wendt L, Chlanda P, Hoenen T. Ebola virus inclusion bodies are liquid organelles whose formation is facilitated by nucleoprotein oligomerization. Emerg Microbes Infect. 2023;12(2):2223727. doi: 10.1080/22221751.2023.2223727.
Fénéant L, Leske A, Günther K, Groseth A. Generation of Reporter-Expressing New World Arenaviruses: A Systematic Comparison. Viruses. 2022;14(7):1563. doi: 10.3390/v14071563.
Wendt L, Brandt J, Ushakov D, …, Pickin MJ, Groseth A, Hoenen T. Evidence for Viral mRNA Export from Ebola Virus Inclusion Bodies by the Nuclear RNA Export Factor NXF1. J Virol. 2022;96(18):e0090022. doi: 10.1128/jvi.00900-22.
Hoenen T, Groseth A. Virus-Host Cell Interactions. Cells. 2022;11(5):804. doi: 10.3390/cells11050804.
Feneant L#, Bodmer BS#, Mettenleiter TC, Groseth A, Hoenen T. Current strategies for Biosafety Level 4 Pathogens. In: New Drug Development for Known and Emerging Viruses. 2022. doi: 10.1002/9783527810697.ch16.
Holzerland J, Fénéant L, Banadyga L, Hölper JE, Knittler MR, Groseth A. BH3-only sensors Bad, Noxa and Puma are Key Regulators of Tacaribe virus-induced Apoptosis. PLoS Pathog. 2020;16(10):e1008948. doi: 10.1371/journal.ppat.1008948.
Hoenen T#, Groseth A#, Feldmann H. Therapeutic strategies to target the Ebola virus life cycle. Nat Rev Microbiol. 2019;17(10):593–606. doi: 10.1038/s41579-019-0233-2.
Martin S, Chiramel AI, Schmidt ML, …, Groseth A, Feldmann H, Hoenen T. A genome-wide siRNA screen identifies a druggable host pathway essential for the Ebola virus life cycle. Genome Med. 2018;10(1):58. doi: 10.1186/s13073-018-0570-1.
Dunham EC, Leske A, Shifflett K, …, Feldmann H, Hoenen T, Groseth A. Life cycle modelling systems support inosine monophosphate dehydrogenase (IMPDH) as a pro-viral factor and antiviral target for New World arenaviruses. Antiviral Res. 2018;157:140–150. doi: 10.1016/j.antiviral.2018.07.009.
Watt A, Moukambi F, Banadyga L, Groseth A, …, Ebihara H, Feldmann H, Hoenen T. A novel life cycle modeling system for Ebola virus shows a genome length-dependent role of VP24 in virus infectivity. J Virol. 2014;88(18):10511–24. doi: 10.1128/JVI.01272-14.
#equally contributing authors