Proteomic and phosphoproteomic profilings reveal distinct cellular responses during Tilapinevirus tilapiae entry and replication

Tilapia lake virus (TiLV) poses a significant threat to global tilapia aquaculture, as it causes high mortality rates and severe economic losses. Nevertheless, the molecular mechanisms of TiLV–host interactions remain poorly understood. We investigated the proteomic and phosphoproteomic changes in E-11 and RHTiB cell lines following TiLV infection. Using mass spectrometry-based analyses, we identified substantial alterations in protein expression and phosphorylation states, highlighted distinct cell line responses. In E-11 cells, TiLV infection suppressed the proteins involved in the Janus kinase–signal transducer and activators of transcription and Fas-associated death domain protein–tumor necrosis factor receptor associated factor pathways, leading to the activation of nucleotide oligomerization domain signaling and cellular apoptosis. The TiLV-infected RHTiB cells showed suppression of the host cellular metabolism through a reduction in protein phosphatase to facilitate early viral entry, while later stages of infection involved increased activity of myosin heavy chain 9 and enhanced host immune responses via the phosphorylation of ribosomal protein L17 and GTPase immunity-associated protein family member 7. These findings suggest that TiLV employs different strategies to manipulate host cellular pathways depending on the cell type. Further studies are essential to validate these findings and ultimately facilitate the development of effective antiviral strategies.