In this study, we revealed a critical role of eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, in regulating T cells during vaccinia virus (VACV) infection. We found that eEF-2K-deficient (eEF-2K⁻/⁻) mice exhibited a significantly higher proportion of VACV-specific effector CD8+ T cells without compromising the development of VACV-specific memory CD8+ T cells. RNA sequencing demonstrated that eEF-2K⁻/⁻ VACV-specific effector CD8+ T cells had enhanced functionality, which improves their capacity to combat viral infection during the effector phase. Moreover, we identified tumor necrosis factor receptor-associated factor 3 (TRAF3) as a critical mediator of the stronger antiviral response observed in eEF-2K⁻/⁻ effector CD8+ T cells. These findings suggest that targeting eEF-2K may provide a novel strategy to augmenting effector CD8+ T cell responses against viral infections.
Keywords: T cell immunity; TRAF3; eEF-2K; effector CD8+ T cells; vaccinia virus (VACV); viral infection.