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Carp express a form of fever
2/9/17
Fish express a form of fever in response to infection. This can save their live. A study, lead by Professor Alain
Vanderplasschen of the Laboratory of Immunology-Vaccinology of Ulg, reveals that it is induced by the same
molecule that triggers fever in humans.
The Laboratory of Immunology
and Vaccinology of the University of Liège led by Professor Alain Vanderplasschen (FARAH) has been
studying for a few years a virus, cyprinid herpesvirus 3 or CyHV-3, causing ravages on a global scale in
common carp farms. Among fish species produced in aquaculture at a global scale, common carp is the third
most important species with an annual production of 4 to 5 million tonnes. It is an essential component in the
diet of millions of humans.
When studying carp infection by CyHV-3, as part of the development of a vaccine, the researchers observed
an unexpected behavior of the fish: fishes grouped themselves near the heating system of their aquarium as
(read : A vaccine against the killer of carp) if they were trying to warm up themself. This behavior is known in
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Reflexions, le site de vulgarisation de l'Université de Liège
cold-blooded animals as behavioral fever. When infected, the animal tries to raise its temperature by moving,
within its environment, to places warmer than those where it habitually resides.
To test the hypothesis that carp infected with CyHV-3 may express behavioral fever, the laboratory builded
aquariums with several compartments within which a temperature gradient was established. Using this system,
researchers found that non-infected carp choose to reside at 24°C, while infected carp moved voluntarily to
the highest temperature of 32°C, resulting in a very rapid healing of the fish. In contrast, infected fish kept
at 24°C all died from the infection. More surprisingly, researchers have identified a mechanism by which the
virus delays the expression of this behavioral fever and has discovered that it is induced by the same molecule
that triggers fever in humans.
The results of this research are published in the prestigious scientific journal Cell Host & Microbe(1). These
results demonstrate that the behavioral fever of cold-blooded animals (ectotherm) and the fever of warmblooded animals (endotherm) rely on common molecules acquired more than 400 million years ago. They
also illustrate the benefits of fever and reveal that changes in the environment (global warming, changes in
ecosystems, etc.) could have a real impact on animal species.
What exactly does this study shows?
1 - The first description of the inhibition of behavioral fever by a pathogen. These results indicate that this
behavior has been acting as a selection pressure on pathogens throughout evolution. Importantly, this
study is also the first report of a vertebrate virus capable of altering the behavior of its host through the
expression of a single gene: To date, there are only two known examples of viral genes that are capable of
affecting the behavior of the infected host, and both examples are genes from baculoviruses (2) that infect
invertebrates.
2 - This research extends the knowledge of the evolutionary and functional relationship between behavioral
fever in ectotherms and fever in endotherms to cytokine mediators that originated more than 400 million
years ago. While a few previous studies have demonstrated that behavioral fever in ectotherms and fever
in endotherms are evolutionarily related based on their regulation at the level of the central nervous system
(prostaglandins), no study has yet demonstrated whether this evolutionary relationship extends to the
cytokine mediators that inform the brain of infections detected in the body by immune cells. The discovery
that Tnf# induces behavioral fever in teleost fish, in addition to its well-known mediation of fever in mammals
(including humans), is truly fascinating. These results further suggest that the ancestral signaling pathway of
behavioral fever regulation in ectotherms evolved in endotherms to regulate the expression of fever.
3 - A new mechanism through which environmental temperature changes can contribute to disease
emergence. This study demonstrates that while an infection can be benign in conditions where the
environment is compatible with the expression of behavioral fever, it can cause a high mortality rate when
the environment does not allow for the expression of this behavior. This finding has important ecological
implications and should be taken into account when considering for example modifications of natural
habitats, introduction of ectotherms in new biotopes and environmental conditions in aquaculture systems.
4 - A new dimension to environmental enrichment for laboratory animals. The study reports the first viral
gene of a vertebrate virus that is capable of altering the behavior of its host. Remarkably, phenotypic
expression of this gene was only observed in conditions that mimicked the temperature gradients of a
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Reflexions, le site de vulgarisation de l'Université de Liège
natural environment, and no phenotypic expression of this gene was observed under standard laboratory
conditions. This study strongly supports the concept that environment enrichment for laboratory animals may
be essential for clarifying the function of numerous viral and cellular genes that do not show a phenotype
under standard laboratory conditions.
5 - A striking example of the effect of the immune system on the central nervous system. An emerging
scientific field is the study of the interactions between the immune system and the central nervous system
(3). This work provides an outstanding example in support of this concept and demonstrates that pathogens
can target these interactions.
6 - A robust example of the beneficial effect of (behavioral) fever on the control of infection. This study is
a remarkable example, in a relevant host-pathogen model, that increased body temperature induced by
infection must be tolerated to allow for control of the pathogen.
In conclusion, this research provides major findings related to host-pathogen interactions and is of interest
for several scientific fields, including virology, immunology, animal behavior, evolution, ecology and even
animal welfare.
(1) Conserved Fever Pathways across Vertebrates: A Herpesvirus Expressed Decoy TNF-a Receptor
Delays Behavioral Fever in Fish, Cell Host & Microbe 21, 244-253, February 8, 2017 - http://
dx.doi.org/10.1016/j.chom.2017.01.010
(2) Science 2011, 333: 1401; PNAS 2005 102: 2584-2589
(3) Nature Reviews Immunology 2011, 9: 625-632
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