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Seminar Details

Acquisition, restriction and inhibition of nervous necrosis virus in a zebrafish larvae model

Date

04/05/2017

Lecturers

Dr. Danny Morick - Morris Kahn Marine Research Centre, University of Haifa

Abstract

Nervous necrosis virus (NNV) is a member of the Betanodavirus genus that causes fatal diseases in over 40 species of fish worldwide. Mortality among NNV-infected fish larvae is almost 100%. In order to elucidate the mechanisms responsible for the susceptibility of fish larvae to NNV, we exposed zebrafish larvae to NNV by bath immersion at 2, 4, 6, and 8 days postfertilization (dpf). Here, we demonstrate that developing zebrafish embryos are resistant to NNV at 2 dpf due to the protection afforded by the egg chorion and, to a lesser extent, by the perivitelline fluid. The zebrafish larvae succumbed to NNV infection during a narrow time window around the 4th dpf, while 6- and 8-day-old larvae were much less sensitive, with mortalities of 24% and 28%, respectively. Following establishment of the infection model, we tested ribavirin as a possible drug that might be considered as an efficient means to reduce the peril of NNV. Ribavirin is a broad-spectrum antiviral drug, mostly used in human clinical practice. Here, we report that treatment of zebrafish larvae with ribavirin prior to infection with nervous necrosis virus (NNV) significantly reduces the mortality caused by the virus during the first 10 days post-infection. The RNA genome of NNV harvested from ribavirin-treated infected larvae contains three synonymous and one single non-synonymous mutation, resulting in the replacement of a serine codon with a glycine codon in the RNA-dependent RNA polymerase gene. Ribavirin treatment of uninfected larvae reduces the basal level of IFNg, but increases the level of IL-1b mRNA expression. Furthermore, infecting larvae with NNV following ribavirin treatment reduces the expression levels of IFNg, IFN-I, Mx, and TNF-a genes, while the expression of IL-1b is increased. These results suggest that cytokine modulation plays an important role in the activity of ribavirin against NNV.

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