Eukaryotic translation elongation factor 1 delta alleviates DNA damage during bovine alphaherpesvirus 1 infection.

importanceBovine alphaherpesvirus 1 (BoAHV-1) is one of the most important viruses that infects cattle and causes significant economic losses. Understanding the critical mechanisms underlying viral pathogenesis is essential for developing novel antiviral strategies.

objectiveTo determine if eukaryotic translation elongation factor-1 Δ (EEF1D) is involved in DNA damage repair in the presence or absence of BoAHV-1 infection by regulating the DNA damage response (DDR) signaling of P53-binding protein 1 (53BP1) and γH2AX.

methodsBovine kidney (MDBK) cells were transfected with EEF1D-specific small interfering RNAs (siRNAs) or a scrambled control siRNA, followed by either a mock infection or virus infection. The effects of EEF1D knockdown on the γH2AX protein levels, γH2AX foci formation, and 53BP1 protein expression and foci formation were evaluated by Western blotting and immunofluorescence assays.

resultssiRNA-mediated EEF1D depletion increased the γH2AX protein levels irrespective of a viral infection and enhanced γH2AX foci formation in BoAHV-1-infected cells. In mock-infected cells, EEF1D knockdown increased the steady-state 53BP1 protein levels and 53BP1 foci formation. In contrast, during viral productive infection, EEF1D knockdown reduced the 53BP1 protein levels despite concurrently suppressing viral protein expression. CONCLUSIONS AND RELEVANCE: EEF1D appears to alleviate BoAHV-1-induced DNA damage, potentially by modulating 53BP1-related DDR signaling. Hence, EEF1D may be a host factor linking viral replication and DDR regulation and may contribute to BoAHV-1 pathogenesis.