Research at the Institute for Integrative Systems Biology (I2SysBio, UV-CSIC) analyses how genetic differences determine the virulence of pathogens such as SARS-CoV-2. The study, carried out in collaboration with the Pasteur Institute, will allow the development of more accurate models of the viruses' evolution in population, whose immunity varies depending on genes and other factors such as age and nutrition.
During the COVID-19 pandemic, some people have been infected several times with the SARS-CoV-2 virus while others have never been infected. Susceptibility to infection by a virus has a genetic basis, but the question here is whether the evolution of the virus also depends on the host's genetics.
This is the question guiding a study carried out by the Institute for Integrative Systems Biology (I2SysBio), a joint centre of the Universitat de València (UV) and the Spanish National Research Council (CSIC), in collaboration with the Pasteur Institute. Its results suggest that it is the immune system as a whole, and not just specific defences, that drives viral diversity and virus evolution. The study is published in the journal Nature Ecology and Evolution.
To carry out this research, the team used an experimental model consisting of the fruit fly (Drosophila melanogaster) and its natural pathogen, the C virus. An experiment on the evolution of the virus was developed, analysing symptom intensity, pathogenesis and genetic variability of evolved viruses. The evolutionary forces - mutation, natural selection and chance - governing the C virus process in each fly genotype were also studied.
"Firstly, we observed how the virus optimises its ability to reproduce and infect the host genotype in which it evolves, depending on the host's defence mechanisms and its response to infection," explains Santiago Elena Fito, who heads the Evolutionary and Systems Virology group at I2SysBio. " Furthermore, we saw that rapid adaptation to the host led to a decrease in the severity of the symptoms," he continues.
Finally, the research team observed that the genetic diversity of the viruses, as well as the mutations they accumulated in their genome, depended on the precise host genotype. "Overall, our results indicate that it is the immune system as a whole, and not the specific defence mechanisms in each case, that determines the genetic diversity of the viruses and their evolution," summarises Santiago Elena.
Asked about the possible consequences of these results for antiviral treatments, the I2SYSBio scientist and co-author of the paper points out that "antiviral drugs act on the virus itself or on its interaction with cells, blocking its entry for example, and not on the immune system. Our complex immune system is stimulated by natural infections and, as it is well known, by vaccines," he concludes.
Conducted in collaboration with Carla Saleh's group at the Institut Pasteur (Paris), the work improves understanding of the implication of genetic differences in host populations on the ability to resist infection and the severity of symptoms produced by viral pathogens. This will allow the development of more accurate models of how viruses may evolve in genetically heterogeneous populations, with levels of immunity varying with age and nutritional status, among other factors.
Reference:
Mongelli V, Lequime S, Kousathanas A, Gausson V, Blanc H, Nigg J, Quintana-Murci L, Elena SF, Saleh MC. Innate immune pathways act synergistically to constrain RNA virus evolution in Drosophila melanogaster. Nat. Ecol. Evol. 2022. DOI: https://doi.org/10.1038/s41559-022-01697-z
Links:
