Antiviral response of adult zebrafish (Danio rerio) during tilapia lake virus (TiLV) infection

Rakus, Krzysztof; Mojzesz, Miriam; Widziolek, Magdalena; Pooranachandran, Niedharsan; Teitge, Felix; Surachetpong, Win; Chadzińska, Magdalena; Steinhagen, Dieter; Adamek, Mikołaj

doi:10.1016/j.fsi.2020.03.040

Cited by 35 publications

(47 citation statements)

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“…In the present study, we prove that mechanisms involved in virus-induced immune response and sickness behavior are evolutionary conserved and fully operating already in the earliest vertebrates-fish. Using TiLV-zebrafish infection models (27,28), we showed that TiLV exhibits neurotropism, remains at a high level in the brain for at least 3 months, and induces the type I IFN-dependent and inflammatory response in the CNS. Subsequently, in infected fish, we observed microglia activation and profound changes in the locomotor and feeding behavior.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, a high level of TiLV was observed in the brain of infected tilapia ( 23 , 25 ), and this was correlated with the clear histopathological changes ( 23 ) and activation of the expression of genes involved in the antiviral immune response in the tilapia brain ( 25 , 26 ). We recently described the TiLV infection model in adult and larvae of zebrafish ( 27 , 28 ), and our virus tropism study revealed that in adult fish the highest viral load of TiLV was found in the brain ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Although the IP challenge did not mimic the natural route of virus infection as compared to the cohabitation challenge model, it provides more benefits, including an equal challenge dose in each individual fish. It also makes it more practical to compare changes in genes in the population, and most of the laboratory-based infection experiments rely on the IP injection of the virus infection [4,15,42,52]. Certainly, the strain of the virus, challenge dose, and species of tilapia could affect the infection's outcome and lead to different mortality rates in these studies.…”

Section: Discussionmentioning

confidence: 99%

“…Given the detection of TiLV at 3 and 6 dpc in the low TiLV fish, we believe that the virus was successful in establishing the infection, but that the infectivity may not be efficient enough to overcome the immune response of the fish. A significant expression of immune-related genes including Mx was reported in zebrafish upon TiLV challenge [52]. Thus, the activation of an antiviral response occurs during early infection and could provide immediate protection.…”

Section: Discussionmentioning

confidence: 99%

Infection of Tilapia tilapinevirus in Mozambique Tilapia (Oreochromis mossambicus), a Globally Vulnerable Fish Species

Waiyamitra

Piewbang

Techangamsuwan

et al. 2021

Viruses

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Tilapia tilapinevirus, or tilapia lake virus (TiLV), is a highly contagious virus found in tilapia and its hybrid species that has been reported worldwide, including in Asia, the Americas, and Africa. In this study, we experimentally challenged Mozambique tilapia (Oreochromis mossambicus) with a virulent TiLV strain, VETKU-TV01, at both low (1 × 103 TCID50/mL) and high (1 × 105 TCID50/mL) concentration. After the challenge, the Mozambique tilapia showed pale skin with some hemorrhage and erosion, lethargy, abdominal swelling, congestion around the eye, and exophthalmos; there was a cumulative mortality rate at 48.89% and 77.78% in the groups that received the low and high concentration, respectively. Quantitative PCR and in situ hybridization confirmed the presence of TiLV in the internal organs of moribund fish. Notably, severe histopathological changes, including glycogen depletion, syncytial hepatic cells containing multiple nuclei and intracytoplasmic inclusion bodies, and infiltration of melanomacrophage into the spleen, were frequently found in the Mozambique tilapia challenged with high TiLV concentration. Comparatively, the infectivity and pathology of the TiLV infection in Mozambique tilapia and red hybrid tilapia (Oreochromis spp.) were found to be similar. Our results confirmed the susceptibility of Mozambique tilapia, which has recently been determined to be a vulnerable species, to TiLV infection, expanding knowledge that the virus can cause disease in this fish species.

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“…In a recent study, high expression of pro‐inflammatory cytokines including IL‐1β and TNF‐α was discovered in the brain and kidneys, while these genes were not as highly expressed in the liver of TiLV‐challenged fish (Mugimba et al., 2019). Another study demonstrated that injecting TiLV in zebrafish induced high type I IFN response (Rakus et al., 2020) Moreover, different genes including erythropoietin isoform X2, double‐stranded RNA‐specific adenosine deaminase isoform X1, bone morphogenetic protein 4 and tapasin‐related proteins as well as differentially expressed mRNAs are involved in immune responses during TiLV infection (Wang, Wang, et al, 2020). Nevertheless, an in‐depth analysis of the role of these genes during TiLV infection is warranted.…”

Section: Tilv Pathogenesismentioning

confidence: 99%

Tilapia lake virus: The story so far

Surachetpong

Roy

Nicholson

2020

Journal of Fish Diseases

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107

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Tilapia lake virus (TiLV) is a highly contagious pathogen that has detrimental effects on tilapia farming. This virus was discovered in 2014 and has received tremendous global attention from the aquaculture sector due to its association with high fish mortalities and its strong economic impact on the tilapia aquaculture industry. Currently, TiLV has been reported in 16 countries, and this number is continuing to rise due to improved diagnostic assays and surveillance activities around the world. In this review, we summarize the up-to-date knowledge of TiLV with regard to TiLV host species, the clinical signs of a TiLV infection, the affected tissues, pathogenesis and potential disease risk factors. We also describe the reported information concerning the virus itself: its morphology, genetic make-up and transmission pathways. We review the current methods for virus detection and potential control measures. We close the review of the TiLV story so far, by offering a commentary on the major TiLV research gaps, why these are delaying future TiLV research and why the TiLV field needs to come together and proceed as a more collaborative scientific community if there is any hope limiting the impact of this serious virus.

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Antiviral response of adult zebrafish (Danio rerio) during tilapia lake virus (TiLV) infection

Cited by 35 publications

References 36 publications

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

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

Infection of Tilapia tilapinevirus in Mozambique Tilapia (Oreochromis mossambicus), a Globally Vulnerable Fish Species

Tilapia lake virus: The story so far

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