Antiviral Activity of Ribavirin against Tilapia tilapinevirus in Fish Cells

Abstract

The outbreak of the novel Tilapia tilapinevirus or Tilapia lake virus (TiLV) is having a severe economic impact on global tilapia aquaculture. Effective treatments and vaccines for TiLV are lacking. In this study, we demonstrated the antiviral activity of ribavirin against TiLV in E-11 cells. Our findings revealed that at concentrations above 100 μg/mL, ribavirin efficiently attenuates the cytopathic effect of the TiLV infection in fish cells. When administered in a dose-dependent manner, ribavirin significantly improved cell survival compared to the untreated control cells. Further investigation revealed that the cells exposed to ribavirin and TiLV had a lower viral load (p < 0.05) than the untreated cells. However, at concentrations above 1000 μg/mL, ribavirin led to cell toxicity. Taken together, our results demonstrate the efficacy of this antiviral drug against TiLV and could be a useful tool for future research on the pathogenesis and replication mechanism of TiLV as well as other piscine viruses.

Tilapia lake virus causes mitochondrial damage: a proposed mechanism that leads to extensive death in fish cells

“…Previous research have demonstrated the susceptibility of various cell lines to TiLV infection, including E-11 cells, a cloned cell line derived from striped snakehead ( Channa striatus , SSN-1) cell line ( Iwamoto et al, 2000 ; Lertwanakarn et al, 2021 ), and primary tilapia ( Oreochromis spp.) cell lines isolated from the brain, heart, and liver ( Eyngor et al, 2014 ; Li et al, 2022a ; Li et al, 2022b ; Yadav et al, 2021 ).…”

“…Previous studies have demonstrated that TiLV can multiply and lead to cell death in various fish cell lines ( Eyngor et al, 2014 ; Lertwanakarn et al, 2021 ; Li et al, 2022a ; Thangaraj et al, 2018 ; Wang et al, 2018 ; Yadav et al, 2021 ). A recent study by Lertwanakarn et al (2021) revealed that TiLV infection caused cytopathic effect (CPE) in E-11 cells within 3 days, while CPE formation in other cell lines may vary between 3 to 11 days post-infection (dpi) ( Li et al, 2022a ; Thangaraj et al, 2018 ; Wang et al, 2018 ; Yadav et al, 2021 ). Transmission electron microscopy (TEM) has revealed that TiLV particles are rounded in shape and approximately 60–110 nm in size ( Eyngor et al, 2014 ; Li et al, 2022a ; Piewbang et al, 2022 ; Thangaraj et al, 2018 ; Wang et al, 2018 ).…”

Structural and functional analysis of the minimal orthomyxovirus-like polymerase of Tilapia Lake Virus from the highly diverged Amnoonviridae family

“…TiLV is now defined as a new species, Tilapia tilapinevirus , in the Tilapinevirus genus, within the Amnoonviridae family, which together with the Orthomyxoviridae , form the Articulavirales order 6 . Whilst the phylogeny of different isolates 7 , detection and pathogenesis of the virus and possible treatments by vaccination 8 or drugs 9 are now being extensively studied, the molecular virology of TiLV is poorly understood, partly due to the current lack of reverse genetics or minigenome systems 10 . In addition, the uniqueness of the putative TiLV encoded proteins, apart from a recognisable polymerase PB1-like subunit, precludes hypotheses as to protein function based on sequence homology or structure prediction using Alphafold 11 or RoseTTAfold 12 .…”

Structural and functional analysis of the minimal orthomyxovirus-like polymerase of Tilapia Lake Virus from the highly divergedAmnoonviridaefamily

“…Whilst the phylogeny of different isolates 5 , detection and pathogenesis of the virus and possible treatments by vaccination 6 or drugs 7 are now being extensively studied, the molecular virology of TiLV is poorly understood, partly due to the current lack of reverse genetics or minigenome systems 8 . In addition, the uniqueness of the putative TiLV encoded proteins, apart from a recognisable polymerase PB1-like subunit, precludes hypotheses as to protein function based on sequence homology or structure prediction using Alphafold 9 .…”