Abstract Successful subversion of translation initiation factors 4E and 4G determines the infection success of potyviruses, the largest group of viruses affecting plants. In the natural variability of many plant species, resistance to potyvirus infection is provided by polymorphisms at 4E and 4G that renders them inadequate for virus hijacking but still functional in translation initiation. In crops where such natural resistance alleles are limited, the genetic inactivation of 4E has been proposed for the engineering of potyvirus resistance. However, recent findings indicate that knockout 4E and 4G alleles may be deleterious for plant health and could jeopardize resistance efficiency in comparison to functional resistance proteins. Here, we explored the cause of these adverse effects by studying the role of the Arabidopsis eIF4E1 , whose inactivation was previously reported as conferring resistance to the potyvirus clover yellow vein virus (ClYVV) while also promoting susceptibility to another potyvirus called turnip mosaic virus (TuMV). We report that eIF4E1 is required to maintain global plant translation and to restrict TuMV accumulation during infection, and its absence is associated with a favoured virus multiplication over host translation. Furthermore, our findings demonstrate that eIF4E1 plays a crucial role in inhibiting the TuMV-induced degradation of the translation initiation factor eIFiso4G1, thereby preventing the generation of a truncated protein. Finally, we demonstrate a role for eIFiso4G1 in TuMV accumulation and in supporting plant fitness during infection. These findings suggest that eIF4E1 counteracts the hijacking of the plant translational apparatus during TuMV infection and underscore the importance of preserving the functionality of translation initiation factors 4E and 4G when implementing potyvirus resistance strategies. Author summary Plants are constantly under threat from viruses that can damage crops and reduce yield. Among these viruses, potyviruses are a major concern, and a small group of genes known as eIF4E are key factors in making a plant susceptible to them. To combat these viruses, it is possible to either use naturally-selected variants of eIF4E that provide resistance, or to disable the gene altogether. However, new research has shown that inactivating eIF4E genes may have unintended consequences for the plant’s development while compromise resistance to other potyviruses. To investigate this further, we focus in this work on the role of the Arabidopsis eIF4E1 whose inactivation confers resistance to one potyvirus, clover yellow vein virus (ClYVV). We looked why this same mutation at eIF4E1 makes the plants more susceptible to another potyvirus, turnip mosaic virus (TuMV). Our study reveals that eIF4E1 acts in safeguarding the plant translational machinery during TuMV infection. By preventing the degradation of the translation initiation protein eIFiso4G1, eIF4E1 enables the plant to maintain its normal translation activity and ultimately prevents the accumulation of virus proteins. Our findings provide valuable insights into how potyviruses hijack the plant’s translation process, and emphasizes the need of preserving the functionality of translation initiation factors when developing potyvirus resistances.

Molecular crosstalk between plant translation initiation complexes influences the outcome of virus infection