Hacking the ribosome to map virus-host associations

Project Information

VirHoX

Grant agreement ID: 101186013

DOI

10.3030/101186013

EC signature date 4 November 2024

Start date 1 February 2025

End date 31 January 2029

Funded under

• The European Innovation Council (EIC)

Total cost

€ 3 560 000,00

EU contribution

€ 3 560 000,00

Coordinated by

UNIVERSITA DEGLI STUDI DI PADOVA
Italy

Periodic Reporting for period 1 - VirHoX (Hacking the ribosome to map virus-host associations)

Reporting period: 2025-02-01 to 2026-01-31

Summary of the context and overall objectives of the project

Viruses are the most abundant biological entities on Earth and play a fundamental role in shaping microbial ecosystems. They influence the health of oceans, soils, animals and humans by controlling microbial populations and altering how microbes function. Despite their importance, one of the major challenges in microbiology and virology is identifying which viruses infect which host organisms. This “virus–host matching” problem limits our ability to understand microbial ecosystems and prevents the development of predictive tools for microbiome research, biotechnology, and environmental monitoring.
Current approaches mainly rely on indirect computational predictions or ecological correlations, which often lack experimental validation. As a result, a large fraction of viruses discovered through modern sequencing technologies remain unlinked to their biological hosts. This gap represents a major barrier to translating viral diversity data into actionable knowledge.
The VirHoX project addresses this challenge by developing a new experimental and computational framework to directly identify interactions between viruses and their hosts. The project introduces VirHo-seq, an innovative sequencing approach designed to capture molecular evidence of viral–host interactions within cells. By combining new molecular tools, advanced sequencing technologies and dedicated bioinformatic pipelines, VirHoX aims to detect and analyse chimeric RNA molecules that reveal direct links between viral genetic material and host ribosomes.
The project brings together complementary expertise in molecular biology, virology, bioinformatics and systems biology to build a complete workflow for viral–host interaction mapping. The work includes the development of new experimental protocols, the creation of dedicated data analysis tools, and the validation of the technology in model microbial systems.
By enabling the direct identification of virus–host relationships, VirHoX will provide a powerful new capability for microbiome science. The results will help researchers move beyond descriptive studies of viral diversity toward a deeper mechanistic understanding of viral infection processes. In the long term, the knowledge generated by the project can support advances in environmental monitoring, microbiome engineering, and biotechnology applications that rely on controlling microbial ecosystems.
VirHoX also contributes to the broader goals of open science and data sharing promoted by the European Union. The project will produce publicly accessible datasets, protocols and analysis tools that can be used by researchers worldwide. By strengthening Europe’s leadership in advanced molecular technologies and viral ecology, VirHoX aims to create new opportunities for scientific discovery and innovation in the rapidly growing field of microbiome research.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the first phase of the VirHoX project, the consortium focused on establishing the experimental and technological foundations required to detect direct interactions between viruses and their microbial hosts. The main objective of this stage was to develop and test the molecular and computational components needed for the VirHo-seq approach, a sequencing strategy designed to identify virus–host associations through chimeric RNA molecules.
A key part of the work involved the development of molecular tools capable of selectively targeting ribosomal RNA molecules and generating controlled cleavage events. These tools are designed to create entry points for the ligation of molecular adapters that allow the capture of RNA fragments originating from both host ribosomes and viral transcripts. Several candidate ribonuclease tools and associated protocols were designed, produced and tested under controlled laboratory conditions to evaluate their efficiency and specificity.
In parallel, the consortium worked on the optimisation of experimental workflows required to generate and enrich RNA molecules that contain both viral and host sequences. This includes the design of specialised RNA adapters, ligation strategies, and purification methods based on magnetic particles that enable the selective recovery of chimeric RNA molecules. Initial protocols for RNA manipulation and ligation reactions were implemented and tested on model bacterial systems to evaluate feasibility and reproducibility.
Another important activity focused on the preparation of sequencing strategies suitable for analysing these complex RNA molecules.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The VirHoX project aims to deliver a novel experimental and analytical framework for identifying direct interactions between viruses and their microbial hosts. The main result expected from the project is the development of VirHo-seq, an innovative sequencing methodology capable of detecting molecular links between viral RNA molecules and host ribosomes. By combining newly developed molecular tools, specialised RNA ligation strategies, and advanced sequencing technologies, VirHoX seeks to provide the first scalable approach for experimentally mapping virus–host interactions in microbial systems.
The expected results include a set of validated molecular protocols for generating and enriching virus–host chimeric RNA molecules, sequencing workflows compatible with both short-read and long-read technologies, and dedicated bioinformatic pipelines for identifying and analysing virus–host interaction signals within sequencing datasets.
To ensure the successful uptake and long-term impact of the project results, several enabling factors will be important. Continued methodological optimisation and validation will be needed to ensure robustness and reproducibility across different biological systems. Further research and demonstration studies will help establish the applicability of the technology to complex microbial communities beyond model organisms.
Open access to protocols, datasets, and analysis tools will also support broader adoption by the scientific community. The project’s commitment to open science and data sharing will facilitate integration with existing microbiome and virology research infrastructures. In addition, the generation of large virus–host interaction datasets may enable the development of predictive computational models and future data-driven tools.
In the longer term, successful maturation of the VirHoX technology may open opportunities for translation into applied research and innovation contexts, including biotechnology, environmental monitoring, and microbiome-based solutions. Continued collaboration with academic, technological, and industrial stakeholders will therefore be important to explore potential pathways for further development, scaling, and integration of the project outcomes into broader research and innovation ecosystems.