The development and use of cultivars genetically resistant to plant viruses, notoriously difficult to treat and combat, is a critical factor for sustainable agriculture. Potyvirus is one of the largest genera of plant viruses responsible for serious diseases in important vegetable and fruit crops. To invade plants, those obligatory parasites have developed tactics to reroute host cellular functions for their own benefits. The completion of the viral cycle results from a complex interplay between virus- and host-encoded factors, also called susceptibility factors. In this scheme, absence or non-adequacy of a single susceptibility factor leads to full or partial resistance to viruses. PotyMove partners were among the first to demonstrate this concept of loss-of-susceptibility resistance genes through the identification of eukaryotic initiation factors as key players in plant-potyvirus interactions, and demonstrated the “transferability” of a potential recessive resistance from the model plant Arabidopsis thaliana to crop plants. Considering the high adaptative potential of plant viruses and resulting resistance breakdown, a more extensive screen of host-virus protein-protein interactors will lead to the identification of new host factors conferring recessive resistance to potyviruses. The ability to combine in the same plant, mutations affecting eukaryotic initiation factors and newly identified genes involved in other steps of the viral cycle, will lead to higher durability of the resistance. In this context, the aim of PotyMove is to identify new plant factors involved in the virus cell-to-cell movement, a key-step of the viral infection. It is considered to be a major putative obstacle to viral exponential expansion in the plant by generating population bottlenecks and thus, an excellent target for resistance: indeed a defection of plant factors required by the virus for its cell-to-cell movement would cause the virus to be confined or restricted to its primary infection focus, thus delaying or preventing its systemic spreading. Also, by increasing the genetic drift, reduced cell-to-cell virus movement could increase resistance durability. Plasmodesmata (PD) are symplasmic tunnels between cells that are the gateway for plant virus movement. Pant virus genome encodes a class of proteins called Movement Protein that interact with host proteins to modify the PD for cell-to-cell movement. For the potyvirus genus, this key step is still very little documented. In particular, no dedicated movement protein has been identified, but three viral proteins with other known functions have been reported to participate in potyvirus movement. Based on a unique consortium with high complementary and transdisciplinary skills (virology, biochemistry, PD proteomics, and genetics), the PotyMove project aims at identifying membrane-associated and/or PD proteins that interact with these three key viral proteins. In parallel, a high throughput genetic approach complementary to PD proteomics will be performed: using forward genetic based on natural diversity or induced diversity, and on quantitative phenotyping, we will identify candidate genes involved in cell-to-cell movement. Furthermore, the PotyMove project aims at providing experimental evidence that the identified candidate genes can afford a broad-range durable resistance to potyviruses and can be transferred to a crop species, tomato, using genome editing strategy. This will be applied to the two initial available candidates, Remorin and PrepP, at the beginning of the PotyMove project. The potential higher durability of those new resistance genes will rely on the fact that they target viral movement proteins known to be under evolutionary constraint and can be further used in crop species for gene pyramiding with previously identified translation initiation factors, in order to implement multifaceted, durable and consumer-acceptable resistances to virus infection.