A thesis from CSIC identifies new strategies for viral diseases control in aquaculture.

Santiago de Compostela, November 2, 2021. The Spanish Research Council (CSIC), through the Immunology and Genomics group of the Institute of Marine Research (IIM), has directed a doctoral thesis whose results allow progress in new strategies for the control of viral diseases in aquaculture, specifically, for nodavirus in European seabass.

The author, Raquel Lama López, carried out the research under the direction of Beatriz Novoa García, CSIC research professor and head of the aforementioned research group. The thesis, “Search for new strategies for controlling viral diseases in aquaculture”, was part of the PhD Program in Advances in Microbial and Parasitic Biology at the University of Santiago de Compostela and had Mª Isabel Santos Rodríguez as tutor. It was recently defended and obtained the qualification of outstanding with mention “cum laude” and “international”.

“Spain ranks fourth in the world classification for bass fishing and third in its aquaculture production. This species is affected by infectious diseases of all kinds, the one that causes the greatest losses is retinopathy and viral encephalopathy, whose causative agent is the nerve necrosis virus, known as nodavirus, which mainly affects the central nervous system and can cause up to 100% mortality in juveniles. The pathological anatomy of infected individuals reveals extensive necrosis of the central nervous system, with vacuolization and neuronal degeneration in the brain and retina of the eye. These damages cause clinical signs that are very characteristic of the disease, such as abnormal swimming behavior, infected individuals show hyperinflation of the swim bladder and swim with downward spiral movements curving their spine, which causes total disorientation in swimming. They also become darker and lose their appetite ”, they explain from the CSIC.

“Currently there are only two vaccines on the market against the RGNVV genotype. For now, the virus is being tackled by extreme prevention measures, avoiding exposure of the crop and reinforcing good management practices “, explains Raquel Lama, who adds “the innate immune response is considered essential to deal with a viral infection”.

In this context, the general objective of the thesis was to explore the topic of the response of seabass to an infection with nodavirus. To this end, the global transcriptome of this nodavirus-infected species was studied using RNAseq, which revealed a high response to stress. “It is also interesting to highlight the possible role of IncRNAs (areas of the genome / transcriptome that until now were thought to have no specific role in the cell) in modulating the transcriptomic response and that a vaccine consisting of a fragment of the protein of betanodavirus, expressed on the surface of bacteria, was successfully used”, highlights the author of the thesis.

The research used different bioinformatic methodologies to study the interactions between seabass and nodavirus (host and pathogen, respectively), for which the complete transcriptomic response of seabass to nodavirus was analysed with the RNA.Seq technique, as well as its possible modulation by non-coding RNAs of the genome (IncRNAs), choosing the brain and kidneys as subjects of study.

“This is the first time that the complete transcriptomic response of seabass to a nodavirus infection has been analysed. An interaction between the neuroendocrine system and the immune system was observed through the hypothalamic-pituitary-interrenal axis during a nodavirus infection. On the other hand, we have described how different IncRNAs could be modulating this transcriptomic response. Furthermore, as a consequence of the neurotropic nature of the nodavirus, the response was greater in the brain than in the kidneys ”, highlights Raquel Lama.

The thesis also developed a prototype of a vaccine for seabass against nodavirus that is characterized, fundamentally, by improving safety and environmental profitability by not requiring adjuvants.

“There are four genotypes within the genus to which the nodavirus belongs that are classified according to the gene sequence that encodes protein C. Most of the vaccines that, to date, have been described against nodavirus, are characterized by using the complete or inactivated virus and by being based on empty capsids, in recombinant protein C or in synthetic peptides derived from protein C ”, says Raquel Lama.

“ Finally, and given the relative difficulty of working with species of high commercial value, we established the zebrafish as a model of infection by nodavirus. In this way, it was possible to determine that the older the larvae, the more complicated it was for them to present symptoms of infection and that a higher mortality of the infected larvae was correlated with a greater expression of the capsid protein of the nodavirus over time”, says Raquel Lama.

“This reaffirms the bases for the zebrafish to be considered a model of infection, not only of nodavirus, but of many other viruses in fish that are difficult to study in vivo due to the difficulties when obtaining the affected species from the market or by their maintenance in the laboratory. Developing a model that allows us to know more quickly and easily the mechanisms through which a virus that causes damage to the central nervous system such as nodavirus acts, opens the door to compare its mechanisms of action with those of viruses that cause encephalopathies in human beings such as the Herpes simplex virus or the varicella zoster virus, and even with the typical developments of neurodegenerative diseases such as Alzheimer’s, and thus try to test therapies that allow us to face common neurodegenerative processes ”, she concludes.

The author

Raquel Lama López (Pazos-Hermos, Ourense, 1990) has a degree in Biology (2008-2013), a Master’s degree in Biotechnology (2013-2015) and a PhD in Biology from the University of Santiago de Compostela (2021).

He has experience in international laboratories – School of Life Sciences at Gwangju Institute Sciences and Technology (GIST, South Korea, 2014), Area of Nanomedicine at the International Iberian Nanotechnology Laboratory (INL, Portugal, 2015) and Laboratorio de Biotecnología y Genómica Acuícola from the Biotechnology Center of the University of Concepción (INCAR, Chile, 2018).

At present, she is hired by the Immunology and Genomics group of the IIM-CSIC in which she is involved in several projects using zebrafish as a study model of the inflammatory process.