Abstract: The unfolded protein response (UPR) serves as a crucial regulatory mechanism that enables eukaryotic cells to mitigate endoplasmic reticulum (ER) stress and plays a significant role in plant antiviral immunity. In this study, we show that V2 protein encoded by the tomato yellow leaf curl virus (TYLCV) induces severe necrotic symptoms in Nicotiana benthamiana and tomato plants. V2 activates the host UPR, and this activation promotes TYLCV infection. Furthermore, we demonstrate that V2 directly interacts with NbFKBP13, a rate-limiting enzyme in protein folding, and inhibits its enzymatic activity. Genetic analysis revealed that NbFKBP13 significantly attenuates V2-induced UPR activation and cell death while enhancing N. benthamiana resistance against TYLCV infection. Similarly, V2 interacts with SlFKBP13, the tomato homolog of NbFKBP13, and SlFKBP13 improves tomato resistance to TYLCV infection. Moreover, both TYLCV infection and V2 expression induce autophagy, a process in which NbFKBP13 plays a crucial role. Notably, the activation of autophagy inhibits TYLCV infection. Our results unveil a molecular mechanism through which the geminivirus V2 protein manipulates the host UPR to facilitate viral infection. These findings significantly advance our understanding of the evolutionary arms race between plants and viruses.

Key words: antiviral defense, autophagy, NbFKBP13, TYLCV, unfolded protein response, V2 protein