eIF4A, a target of siRNA derived from rice stripe virus, negatively regulates antiviral autophagy by interacting with ATG5 in Nicotiana benthamiana

Abstract

Autophagy is induced by viral infection and has antiviral functions in plants, but the underlying mechanism is poorly understood. We previously identified a viral small interfering RNA (vsiRNA) derived from rice stripe virus (RSV) RNA4 that contributes to the leaf-twisting and stunting symptoms caused by this virus by targeting the host eukaryotic translation initiation factor 4A (eIF4A) mRNA for silencing. In addition, autophagy plays antiviral roles by degrading RSV p3 protein, a suppressor of RNA silencing. Here, we demonstrate that eIF4A acts as a negative regulator of autophagy in Nicotiana benthamiana. Silencing of NbeIF4A activated autophagy and inhibited RSV infection by facilitating autophagic degradation of p3. Further analysis showed that NbeIF4A interacts with NbATG5 and interferes with its interaction with ATG12. Overexpression of NbeIF4A suppressed NbATG5-activated autophagy. Moreover, expression of vsiRNA-4A, which targets NbeIF4A mRNA for cleavage, induced autophagy by silencing NbeIF4A. Finally, we demonstrate that eIF4A from rice, the natural host of RSV, also interacts with OsATG5 and suppresses OsATG5-activated autophagy, pointing to the conserved function of eIF4A as a negative regulator of antiviral autophagy. Taken together, these results reveal that eIF4A negatively regulates antiviral autophagy by interacting with ATG5 and that its mRNA is recognized by a virus-derived siRNA, resulting in its silencing, which induces autophagy against viral infection.

Autophagy in plant viral infection

“…Interestingly, Zhang et al . [69] reported that eIF4A interferes with the ATG5–ATG12 interaction by interacting with ATG5 to inhibit autophagy. These results suggest that the down‐regulated mRNA of eIF4A, which is recognized and degraded by the vsiRNA derived from RSV, results in the activation of autophagy to counter viral infection.…”

“…Further, Shi et al [68] identified that a viral small interfering RNA (vsiRNA) derived from RSV RNA4 contributes to the leaftwisting and stunting symptoms by targeting host eukaryotic translation initiation factor 4A (eIF4A) mRNA for silencing. Interestingly, Zhang et al [69] reported that eIF4A interferes with the ATG5-ATG12 interaction by interacting with ATG5 to inhibit autophagy. These results suggest that the down-regulated mRNA of eIF4A, which is recognized and degraded by the vsiRNA derived from RSV, results in the activation of autophagy to counter viral infection.…”

“…Both ATI1 and ATI2 interact with AGO1 and associate with P0 on the ER, and the complex including ATI1, ATI2 and AGO1 is loaded into ER-associated vesicles that are moved to the vacuole for autophagic degradation following P0 expression. Autophagy is also reported to be used by RSV to counteract plant defense, although disruption of autophagy enhances RSV infection [56,69]. The remorin protein NbREM1 is a plant-specific membrane-associated protein and plays crucial roles in plant-pathogen interactions, and its S-acylated form is required to restrict RSV cell-to-cell trafficking.…”

A Review of Vector-Borne Rice Viruses

“…Besides, silencing of NbeIF4A activates autophagy and inhibits RSV infection by facilitating autophagic degradation of p3. Further study indicated that overexpression of vsiRNA-4A, a viral siRNA derived from RSV RNA4, targets eIF4A mRNA for cleavage, thus leading to induced autophagy [ 122 ]. Recently, RSV activates the bZIP17/28 branch of unfolded protein response signaling pathway to promote viral infection [ 123 ].…”

Autophagy in the Lifetime of Plants: From Seed to Seed

“…Furthermore, autophagy also plays an antiviral role in negative-strand RNA virus infection. The viral suppressors of the RNAi (VSR) protein P3 from rice stripe virus (RSV) can interact with NbPI3P and can be degraded by autophagy, thereby inhibiting RSV infection [ 83 ]. In this process, eukaryotic translation initiation factor 4A (eIF4A) acts as a repressor by interacting with ATG5 to leave the ATG5–ATG12 interaction to inhibit autophagy [ 84 ].…”