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Human cells have few barriers to prevent the entry of animal viruses

  • Scientific Culture and Innovation Unit
  • January 23rd, 2025
(From left to right). Jéremy Dufloo, Iván Andreu-Moreno, Jorge García-Moreno i Rafael Sanjuán.
(From left to right). Jéremy Dufloo, Iván Andreu-Moreno, Jorge García-Moreno i Rafael Sanjuán.

A research team from the Institute of Integrative Systems Biology (I2SysBio), a joint centre of the University of Valencia and the Spanish National Research Council (CSIC), asserts that the proteins responsible for mediating the entry of animal viruses also function in human cells, meaning the barriers to interspecies transmission are fewer than previously thought. The team explains in the journal Nature Microbiology that they have developed safe viral prototypes using RNA fragments from 102 enveloped viruses from 14 different families and have tested their infectivity with more than 5,000 combinations.

"The fact that a virus enters our cells does not automatically mean it will cause a disease. For that to happen, it requires a combination of additional factors that we are still investigating. Our work marks an important step in identifying which viruses pose a greater risk to humans and how we can better prepare ourselves against them", explains Rafael Sanjuán, I2SysBio researcher and professor of Genetics at the University of Valencia.

To study the infective capacity of certain viruses, the researchers constructed pseudoviruses —safe imitations of real viruses— using components such as their receptor-binding protein (RBP), which is key for their entry into cells. These were inoculated into human cells. The team also explored the role of proteases and carbohydrates in the infection process within cells.

"This allowed us to study whether certain animal viruses, which had never been analysed in detail before, can enter human cells. The results showed that many animal viruses have this capability. This means that we are potentially exposed to a large number of viruses", adds Rafael Sanjuán, who has published over 100 research articles on viruses and evolution.

This research, titled "Experimental Virology for Assessing Disease Emergence Risks" (EVADER), is part of a project investigating the threats posed by viruses from wildlife that received €2.43 million from the European Research Council in 2021 under the Advanced Grants scheme, the largest funding category awarded by Europe's primary research body. The importance of this research lies in the fact that many diseases, such as AIDS, influenza or COVID-19, originated by jumping from animals to humans. Rafael Sanjuán has received almost uninterrupted funding from the ERC over the past 15 years.

This process of viruses crossing over from animals into humans, known as zoonosis, is more common among enveloped RNA viruses because they have a high capacity for adaptation, interspecies spread and pandemic potential. The research cannot predict which virus might cause the next pandemic: "It is very difficult because there are many factors involved, such as ecology, genetics, the immune system and evolution. Moreover, it is estimated that there are tens of thousands of viruses that infect mammals, many of which could potentially infect humans", explains Rafael Sanjuán. He points out that thanks to metagenomics, many viruses are now known but only from their genetic material, as they have never been cultivated or directly studied in the laboratory.

New human viruses that cause diseases originating in animals are a growing concern. Their emergence is also a poorly understood process. The COVID-19 pandemic demonstrated that combating wildlife viruses is an urgent challengeand, as a result, the scientific community has been launching large-scale sequencing programmes to characterise wildlife viruses. This new research reveals repeatable evolutionary pathways that could improve outbreak predictions and enhance the feasibility of using broad-spectrum antiviral therapies to combat emerging viruses.

 

Article reference: Dufloo, J., Andreu-Moreno, I., Moreno-García, J. et al. Receptor-binding proteins from animal viruses are broadly compatible with human cell entry factors. Nat Microbiol (2025). https://doi.org/10.1038/s41564-024-01879-4