Dissecting the localization of Tilapiatilapinevirus in the brain of the experimentally infected Nile tilapia, Oreochromisniloticus (L.)

Abstract

Tilapia tilapinevirus or tilapia lake virus (TiLV) is an emerging virus that inflicts significant mortality on farmed tilapia globally. Previous studies reported detection of the virus in multiple organs of the infected fish; however, little is known about the in‐depth localization of the virus in the central nervous system. Herein, we determined the distribution of TiLV in the entire brain of experimentally infected Nile tilapia. In situ hybridization (ISH) using TiLV‐specific probes revealed that the virus was broadly distributed throughout the brain. The strongest positive signals were dominantly detected in the forebrain (responsible for learning, appetitive behaviour and attention) and the hindbrain (involved in controlling locomotion and basal physiology). The permissive cell zones for viral infection were observed mostly to be along the blood vessels and the ventricles. This indicates that the virus may productively enter into the brain through the circulatory system and widen broad regions, possibly through the cerebrospinal fluid along the ventricles, and subsequently induce the brain dysfunction. Understanding the pattern of viral localization in the brain may help elucidate the neurological disorders of the diseased fish. This study revealed the distribution of TiLV in the whole infected brain, providing new insights into fish–virus interactions and neuropathogenesis.

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

“…Similarly, dissociation and degeneration within the infected sites of the brain of TiLV-infected tilapia has also been demonstrated (36). In adult zebrafish, we only observed enlarged blood vessels in the brain of TiLV-infected fish (14 dpi; data not shown).…”

“…Histopathological analysis of the brain showed clear pathological changes in the TiLV-infected larvae, including the degeneration in the neuropil and disintegration of the perikarya. Similarly, dissociation and degeneration within the infected sites of the brain of TiLV-infected tilapia has also been demonstrated ( 36 ). In adult zebrafish, we only observed enlarged blood vessels in the brain of TiLV-infected fish (14 dpi; data not shown).…”

“…In tilapia, it has been reported that during TiLV infection, viral titer in the brain is gradually increasing up to 17 dpi and remained high on 34 dpi (last studied time point). Moreover, ISH analysis revealed that TiLV was widely distributed in various parts of the tilapia brain, with the strongest signal observed in the forebrain (involved in learning and regulation of food intake) and the hindbrain (responsible for controlling locomotion and basal physiology) ( 36 ). In our study, the molecular analysis did not reveal any differences in the viral load in a specific part of the brain (forebrain, midbrain, and hindbrain) of adult zebrafish, while TEM analysis confirmed the presence of the virions in all three parts of the brain.…”

“…Both “brain-borne” and circulating proinflammatory cytokines may act at the level of CNS and induce sickness behavior ( 4 , 5 , 41 ). Previous studies have demonstrated that TiLV-infected tilapia displays a loss of appetite, lethargy, erratic swimming, loss of balance, swimming at the water surface, stoppage of schooling, or swirling ( 24 , 29 , 36 , 42 ). Here, we demonstrated that zebrafish infected with TiLV had reduced velocity, shortened travelled distance, reduced time in-motion, and increased time spent at the bottom zone of aquaria.…”

Efficacy of heat-killed and formalin-killed vaccines againstTilapia tilapinevirusin juvenile Nile tilapia (Oreochromis niloticus)

“…Cumulative mortalities of up to 80% have been reported for farmed tilapia in Israel, while in a report from Ecuador the percentage of mortalities appeared to fluctuate from 10-20% up to 80% depending on the fish strain when tilapia fish were transferred to grow out cages, with fish dying within 4-7 days of transfer (Eyngor et al, 2014; Ferguson et al, 2014). The mortality levels caused by TiLV infection in Thailand were also variable, ranging from 20-90% (Dong et al, 2017c), and experimental infections also tended to result in high levels of mortality (66-100%) (Behera et al, 2017; Dinh-Hung et al, 2021; Eyngor et al, 2014; Tattiyapong et al, 2017). All of these reports suggest that TiLV is highly virulent and will cause significant mortality loss if introduced to a production site.…”