Sugarcane streak mosaic virus P1 protein inhibits unfolded protein response through direct suppression of bZIP60U splicing

The unfolded protein response (UPR) is a cell-designated strategy that maintains the balance of protein folding in the endoplasmic reticulum (ER). UPR features a network of signal transduction pathways that reprogram the transcription, mRNA translation, and protein post-translational modification to relieve the ER stresses from unfolded/misfolded proteins. Infection with plant viruses can induce the UPR, and activated UPR often promotes plant viral infections in turn. However, the mechanism used by plant viruses to balance UPR and achieve robust infection remain largely unknown. In this study, P1(SCSMV) was identified as a virus-encoded RNA silencing suppressor (VSR). Heterologous overexpression of P1(SCSMV) via potato virus X (PVX) was found lead to programmed cell death (PCD) in Nicotiana benthamiana. Furthermore, P1(SCSMV) was also found to inhibit the PVX infection-triggered UPR by downregulating UPR-related genes and directly induced the distortion and collapse of the ER polygonal meshes on PVX-P1(SCSMV) infected N. benthamiana. Moreover, self-interaction, VSR activity, UPR inhibition, and cell death phenotype of P1(SCSMV) were also found to be dependent on its bipartite nuclear localization signal (NLS) ((RKRKLFPRIPLK262)-R-251). P1(SCSMV) was found to directly bind to the stem-loop region of NbbZIP60U via its NLS and inhibit the UPR pathways, ultimately resulting in a PCD phenotype in PVX-P1(SCSMV) infected N. benthamiana leaves. This study also revealed the balancing role of potyviruses encoded P1(SCSMV) in the UPR pathway to achieve robust viral infection. This may represent a novel virulence strategy for plant viruses.