The eukaryotic translation elongation factor 1 (eEF1) family exhibits critical roles in RNA viral infection beyond its canonical function in protein synthesis. This review analyzes the structural characteristics of eEF1A and the eEF1B complex, and their regulatory mechanisms during viral infection. eEF1A impacts viral replication by stabilizing viral RNA-dependent RNA polymerase (RdRp) complexes, modulating genomic RNA synthesis, and facilitating viral assembly through cytoskeletal regulation. eEF1B subunits contribute through enhancing viral mRNA translation, regulating nuclear transport of viral components, and mediating post-translational modifications. The high conservation of eEF1 proteins across species and their involvement in multiple stages of viral replication establish them as promising broad-spectrum antiviral targets. Current eEF1-targeting compounds like plitidepsin demonstrate efficacy against diverse viral families, though therapeutic development faces challenges in balancing antiviral activity with host toxicity. This review provides a theoretical foundation for developing novel antiviral strategies targeting host–virus interaction interfaces and offers insights into addressing emerging infectious diseases.

The novel H10N3 avian influenza virus (AIV) has infected four individuals since 2021 and caused severe respiratory damage, posing a significant threat to public health. However, its pathogenic mechanisms remain poorly understood. Our findings revealed that H10N3 infection induces severe lung damage and causes death in mice, even at low doses. The elevated levels of multiple pro-inflammatory factors in the bronchoalveolar lavage fluid were significantly increased during infection, displaying hallmarks of a cytokine storm. Transcriptome sequencing further revealed systematic activation of inflammation-related pathways, predicting that viral infection induces multiple forms of programmed cell death, including apoptosis, pyroptosis, and necroptosis. Protein-level validation showed that the activation of key cell death markers, including Caspase-3, GSDMD, and MLKL, significantly increased as the infection progressed, with their dynamic changes correlating strongly with the expression pattern of viral proteins. This study elucidates the central role of the synergistic effect between the cytokine storm and multiple cell death pathways in H10N3 pathogenesis. These findings not only advance our understanding of the pathogenic mechanisms of AIVs but also provide a critical theoretical basis for the development of targeted therapeutic strategies.