The doctoral research of Valeria Aguilar Quiñones shows that resistance is not determined by genes alone, but also by the interaction between the virus, the host, and the environment.
Can a virus learn to bypass a host’s natural defenses? This is one of the questions Valeria Aguilar Quiñones explored in her PhD research. Her findings demonstrate that virus resistance is not a fixed trait controlled solely by genetics. Rather, the outcome of disease is the result of a complex interplay between the virus, the host, and the environment.
One of the most important findings of the dissertation is that genetic changes in the virus can influence how effective the host’s resistance is. Through studies of infectious pancreatic necrosis virus (IPNV), a disease-causing virus in Atlantic salmon, Quiñones investigated a viral isolate capable of causing disease even in fish carrying a well-known genetic resistance to IPN.
This finding shows that even strong genetic resistance can be challenged when the virus evolves. At the same time, Quiñones found that the ease with which resistance can be overcome depends on the biological mechanisms underlying that resistance. Resistance based on minor genetic differences may be easier for a virus to circumvent than resistance resulting from more extensive genetic changes.
More than just genes
Virus resistance is often explained in terms of genetics. However, this doctoral work demonstrates that factors within cells also play a crucial role.
To investigate this, Quiñones developed a new Atlantic salmon cell line called ASSF. This new cell line provides researchers with an important tool for studying how viruses infect salmon cells under laboratory conditions.
The experiments showed that not all cells respond to viral infection in the same way, even when they appear identical. Some cells were infected more readily than others, and susceptibility could change over time. This suggests that a cell’s physiological state influences how successfully a virus can establish an infection.
According to the research, factors such as which genes are active within the cell, the availability of receptors on the cell surface, and the organization of tissues may all be important determinants of disease outcome.
Barriers to gene delivery in cells
The dissertation also examined the use of lentiviral vectors, a technology commonly used to deliver genes into cells. While these tools are widely applied in research on human cells, they are less effective in salmon cells.
Quiñones found that gene delivery was both less efficient and more variable in Atlantic salmon cells than in human cells. The results suggest that natural cellular defense mechanisms limit the effectiveness of this technology.
Nevertheless, the study showed that certain interventions could improve outcomes. Techniques such as spinfection, heat shock, and alterations in the function of an antiviral gene increased the efficiency of gene delivery in ASSF cells. At the same time, experiments revealed that some fish cell lines were considerably more permissive than others.
These findings indicate that such barriers are not equally strong across all cell types and can be influenced by the biological state of the cells.
A new perspective on virus resistance
Taken together, the dissertation provides a more comprehensive understanding of how viral infections develop in Atlantic salmon. The findings may have implications for both future research and the assessment of disease risk in the aquaculture industry. The research highlights that resistance effective against one viral variant does not necessarily provide the same level of protection against newly emerging variants.
The work also demonstrates that lentiviral gene delivery is feasible in salmon cells, although the technology still encounters biological obstacles. As such, the dissertation opens new avenues for research aimed at understanding and partially overcoming these barriers.
Through her work, Quiñones shows that the battle between virus and host has no permanent winner. It is a continuous biological arms race in which even small changes can have major consequences.
Valeria Aguilar Quiñones will defend her doctoral thesis, entitled "Viral resistance in Atlantic salmon: insights from viral, cellular and functional studies", on 14 August at the Norwegian University of Life Sciences (NMBU).
Her principal supervisor has been Dr. Victor Boyartchuk, Norwegian University of Life Sciences. Co-supervisor: Dr. Jacob Seilø Torgersen, AquaGen AS.