Tilapia Lake Virus-Induced Neuroinflammation in Zebrafish: Microglia Activation and Sickness Behavior

Abstract

In mammals, the relationship between the immune system and behavior is widely studied. In fish, however, the knowledge concerning the brain immune response and behavioral changes during brain viral infection is very limited. To further investigate this subject, we used the model of tilapia lake virus (TiLV) infection of zebrafish (Danio rerio), which was previously developed in our laboratory. We demonstrated that TiLV persists in the brain of adult zebrafish for at least 90 days, even when the virus is not detectable in other peripheral organs. The virions were found in the whole brain. During TiLV infection, zebrafish displayed a clear sickness behavior: decreased locomotor activity, reduced food intake, and primarily localizes near the bottom zone of aquaria. Moreover, during swimming, individual fish exhibited also unusual spiral movement patterns. Gene expression study revealed that TiLV induces in the brain of adult fish strong antiviral and inflammatory response and upregulates expression of genes encoding microglia/macrophage markers. Finally, using zebrafish larvae, we showed that TiLV infection induces histopathological abnormalities in the brain and causes activation of the microglia which is manifested by changes in cell shape from a resting ramified state in mock-infected to a highly ameboid active state in TiLV-infected larvae. This is the first study presenting a comprehensive analysis of the brain immune response associated with microglia activation and subsequent sickness behavior during systemic viral infection in zebrafish.

Tilapia lake virus disease: Vaccine strategies to control the threat to tilapia aquaculture

“…33,34 Recently, Mojzesz et al revealed that TiLV could persist in the brains of infected zebrafish for 90 dpi, inducing a strong antiviral inflammatory response and increasing the expression of microglia/macrophage gene markers. 56 Although insight from host-pathogen interactions from the zebrafish model are helpful, further investigation using tilapia, a naturally susceptible host, is still required to understand the immunological mechanisms that lead to the survival of the fish after infection.…”

Fish Behavior as a Neural Proxy to Reveal Physiological States

“…Bacterin-treated fish showed alterations of brain activities and lowered social preferences and exploratory behaviors toward novel objects ( Kirsten et al, 2018b ). Tilapia lake virus infection caused decreases in zebrafish locomotion and food intake, abnormal swimming patterns, and histopathological changes in the zebrafish brain ( Mojzesz et al, 2021 ). This suggests that the immune system may mediate defensive responses at the behavioral level to minimize potential risks of infection and reallocate energy to healing.…”

Tilapia lake virus (TiLV) causes severe anaemia and systemic disease in tilapia

“…(Yamkasem et al, 2021). Tilapia lake virus can infect other fish species including Giant gourami ( Osphronemus goramy ), wild river barb ( Barbonymus schwanenfeldii ) and Zebrafish ( Danio rerio ) (Abdullah et al, 2018; Chiamkunakorn et al, 2019; Jaemwimol et al, 2018; Mojzesz et al, 2021; Rakus et al, 2020). The common clinical signs of TiLV infection are lethargy, anorexia, swimming at the water surface, skin haemorrhage and discolouration, exophthalmos, scale protrusion and abdominal distension (del‐Pozo et al, 2017; Eyngor et al, 2014; Surachetpong et al, 2017).…”