The Potyvirus genus is one of the largest genera of plant RNA viruses responsible for serious diseases in crops worldwide. As potyviruses hijack the host secretory pathway and plasmodesmata (PD) for their transport, the goal of this study was to identify membrane and/or PD-proteins that interact with the 6K2 protein, a potyviral protein involved in replication andcell-to-cell movement of turnip mosaic virus (TuMV). Using Split-ubiquitin membrane Y2H assays we screened an Arabidopsis cDNA library for interactors of TuMV-6K2. We isolated AtHVA22a (Hordeum vulgare abscisic acid responsive gene 22) that belongs to a multigenic family of proteins homologous to DP1/Yop1 family proteins in yeast and interactorsof reticulons. The role of HVA22 proteins in plants are not well-known, except the role in blast disease resistance in rice. Interestingly, proteomics analysis of PD fractions showed that AtHVA22a is highly enriched in Arabidopsis plasmodesmata proteome. We confirmed the interaction between 6K2 and AtHVA22a in yeast, as well as in planta by using bimolecularfluorescence complementation (BiFC) and showed that the interaction occurs at the level of the viral replication complexes (VRC) during TuMV infection. Finally, we showed that the propagation of TuMV in plants is increased when AtHVA22a is overexpressed but slowed down upon mutation of AtHVA22a by CRISPR-Cas9. Altogether, our results indicate that AtHVA22a plays an agonistic effect on TuMV propagation.Read less <