The Institute for Integrative Systems Biology, located at the Science Park, describes a viral infection process from birth to sexual maturity with the highest temporal resolution achieved to date. The work, published in 'Science Advances', opens the door to search for new antiviral therapeutic targets based on the mechanisms of response to chronic infection
Describing the response of a living organism to a chronic virus infection, from birth to sexual maturity. This is the milestone achieved by a research group at the Institute for Integrative Systems Biology (I2SysBio), located at the University of Valencia Science Park, and published in the prestigious journal Science Advances. Using different techniques they have studied how the nematode Caenorhabditis elegans, a worm widely used as an experimental model, controls the infection of the Orsay virus from its birth to its reproductive phase, with the highest temporal resolution so far in a whole organism.
The study focused on describing the accumulation and localization of the virus in the host organism's tissues, and on analyzing how its genes responded during infection. To do this, they analyzed the entire transcriptome, the set of RNA molecules, comparing the expression of genes from infected and uninfected animals. Caenorhabditis elegans is widely used in research because of its genetic similarity to humans, with more than 80% of its proteins being similar. Its natural parasite, Orsay virus, is an RNA virus first described in 2011 and similar to other human pathogens such as those causing avian influenza or COVID-19.
“We have described a viral infection process with the highest temporal resolution to date”
“The use of the model organism C. elegans has allowed us to observe the complex responses that occur in a whole organism when it is infected by a virus,” describe Victoria García Castiglioni and María José Olmo Uceda, CSIC researchers at I2SysBio and authors of the study. “The use of a whole organism, although it adds complexity to the results, also gives us a more realistic account of what happens in natural situations,” they point out.
Through a multidisciplinary approach, using techniques from virology, genetics, transcriptomics and molecular, computational and developmental biology, they have managed to describe this chronic infection process with an unprecedented level of detail and temporal resolution. Thus, for example, they have classified the response genes to viral infection into different basic profiles: early response genes that are activated immediately after infection; genes whose profile correlates with the amount of virus throughout the organism's development; or late response genes that are only activated in the last phase of infection.
In addition, they have made a temporal description of the virus cycle; identified the genes that the virus uses to its advantage and those that the animal uses as a defense; and marked specific response genes to viral infection, in contrast to nonspecific responses to infection with other pathogens. “We have described a viral infection process with the highest temporal resolution to date,” summarize the study authors.
Learning from a successful defense strategy
The time series spans from the moment of infection after birth to the arrival at reproductive age (between three and five days), passing through all phases of individual development. “This has allowed us to classify the infection process into different stages depending on the behavior of the virus and the type of host responses,” say the CSIC researchers.
“Viruses that cause severe acute diseases are the most studied, due to their socioeconomic impact. However, we live with chronic viruses whose persistent infections accompany us throughout our lives,” reveals Santiago F. Elena, a researcher in the Evolutionary and Systems Virology group at I2SysBio who conducted the study. “This is the case we have studied, where the first infection of the virus does not cause severe acute symptoms and shows an example of a successful defense strategy that, without eliminating the virus from the organism, is able to control it”.
The results, which have just been published in the prestigious scientific journal Science Advances, together with the genetic similarity between C. elegans and humans, which is already used in studies of cancer, neuroscience, dermatology and the development of pharmacological applications, “open the door to search for new antiviral therapeutic targets with future clinical applications,” says the I2SysBio researcher.
Castiglioni, V.G., Olmo-Uceda, M.J., Villena-Giménez, A., Muñoz-Sánchez, J.C., Legarda, E.C., Elena, S.F. (2024) Story of an infection: viral dynamics and host responses in the Caenorhabditis elegans-Orsay virus pathosystem. Science Advances. DOI: 10.1126/sciadv.adn5945