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Integrating mass spectrometry, network and structure modelling to study virus-host interactions in Arenaviruses
Summary
Arenaviruses are a diverse group of viruses that typically infect rodents but can also cause serious illness in humans. Some, like the Lassa virus, are known for causing dangerous hemorrhagic fevers, while others, such as LCMV, can lead to meningitis. Lassa fever is particularly concerning in West Africa and is considered a public health priority by the WHO. These viruses depend heavily on human host proteins to replicate and spread, since they carry only a small number of their own viral proteins.
This project focuses on understanding how arenaviruses interact with host proteins during infection. Researchers will compare several arenaviruses to identify shared strategies and molecular interactions they use to hijack the host’s cellular machinery. Using advanced bioinformatics and mass spectrometry, the team will map and validate these virus-host protein interactions, build structural models of the complexes, and identify possible weak spots in the viral proteins that could be targeted by future treatments.
By identifying common host factors and interaction sites, this research aims to uncover fundamental mechanisms that arenaviruses rely on - insights that could support the development of broad-spectrum antiviral strategies.
Our Work Packages (WP):
WP1: Develop virus-host protein interaction network for human arenaviruses (ArenaInt).
WP2: Verify selected, predicted virus-host protein complexes.
WP3: Model mutations of MS-validated virus-host protein complexes and inhibitor peptide design.
WP4: Determine interaction interfaces and impact of mutations.
The four work packages aim to uncover and model key arenavirus–host protein interactions, verify them experimentally, and identify peptide targets - building a flexible pipeline that can be applied to other emerging viruses and guide future antiviral development.
Team
Prof. Dr. Maya Topf
Principal Investigator
E-mail address:
Phone: +49 040 8998 87660
Prof. Dr. Charlotte Uetrecht
Principal Investigator
E-mail address:
Phone: +49 (0) 40 8998 - 87585
Group Topf
The group Integrative Virology is based at the Centre for Structural Systems Biology (CSSB).
Group Uetrecht
The group Dynamics of Virual Structures is based at the Centre for Structural Systems Biology (CSSB).
Project related publications
Sänger L, Williams HM, Yu D, Vogel D, Kosinski J, Rosenthal M, Uetrecht C. RNA to Rule Them All: Critical Steps in Lassa Virus Ribonucleoparticle Assembly and Recruitment. J Am Chem Soc. 2023 Dec 27;145(51):27958–27974. doi: 10.1021/jacs.3c07325.
Kopicki JD, Saikia A, Niebling S, Günther C, Anjanappa R, Garcia-Alai M, Springer S, Uetrecht C. Opening opportunities for Kd determination and screening of MHC peptide complexes. Commun Biol. 2022 May 23;5(1):488. doi: 10.1038/s42003-022-03366-0.
Malhotra S, Joseph AP, Thiyagalingam J, Topf M. Assessment of protein-protein interface in cryo-EM derived assemblies. Nat Commun. 2021;12(1):3399. doi:10.1038/s41467-021-23692-x.
Krichel B, Bylapudi G, Schmidt C, …, Madhugiri R, Ziebuhr J, Uetrecht C. Hallmarks of and non-structural protein 7+8 complexes. Sci Adv. 2021;7(10). doi:10.1126/sciadv.abf1004.
Kryshtafovych A, Schwede T, Topf M, Fidelis K, Moult J. Critical assessment of methods of protein structure prediction (CASP)-Round XIV. Proteins. 2021;89(12):1607–1617. doi:10.1002/prot.26237.
Krichel B, Falke S, Hilgenfeld R, Redecke L, Uetrecht C. Processing of the SARS-CoV p1a/ab nsp7-10 region. Biochem J. 2020;477(5):1009–1019. doi:10.1042/BCJ20200029.
Hernández Durán A, Grünewald K, Topf M. Conserved Central Intraviral Protein Interactome of the Herpesviridae Family. mSystems. 2019;4(5). doi:10.1128/mSystems.00295-19.
Hernández Durán A, Greco TM, Vollmer B, Cristea IM, Grünewald K, Topf M. Protein interactions and consensus clustering analysis uncover insights into herpesvirus virion structure and function relationships. PLoS Biol. 2019;17(6):e3000316. doi:10.1371/journal.pbio.3000316.
Smelt CLC, Sanders VR, Newcombe J, …, Sheppard TD, Topf M, Millar NS. Identification by virtual screening and functional characterization of novel positive and negative allosteric modulators of the α7 nicotinic acetylcholine receptor. Neuropharmacology. 2018;139:194–204. doi:10.1016/j.neuropharm.2018.07.009.
Ashford P#, Hernandez A#, Greco TM#, …, Grünewald K, Shepherd A, Topf M. HVint: A Strategy for Identifying Novel Protein-Protein Interactions in Herpes Simplex Virus Type 1. Mol Cell Proteomics. 2016;15(9):2939–2953. doi:10.1074/mcp.M116.058552.
#equally contributing authors