Multiple ER-to-nucleus stress signaling pathways become active duringPlantago asiatica mosaic virusandTurnip mosaic virusinfection inArabidopsis thaliana

Abstract

SummaryEndoplasmic reticulum (ER) stress due to biotic or abiotic stress activates the unfolded protein response (UPR) to restore ER homeostasis. The UPR relies on multiple ER-to-nucleus signaling factors which mainly induce the expression of cytoprotective ER-chaperones. The inositol requiring enzyme (IRE1) along with its splicing target, bZIP60, restrict potyvirus, and potexvirus accumulation. Until now, the involvement of the alternative UPR pathways and the role of UPR to limit virus accumulation have remained elusive. Here, we used the Plantago asiatica mosaic virus (PlAMV) and the Turnip mosaic virus (TuMV) to demonstrate that the potexvirus triple gene block 3 (TGB3) protein and the potyvirus 6K2 protein activate the bZIP17, bZIP28, bZIP60, BAG7, NAC089 and NAC103 signaling in Arabidopsis thaliana. Using the corresponding knock-out mutant lines, we demonstrated that these factors differentially restrict local and systemic virus accumulation. We show that bZIP17, bZIP60, BAG7, and NAC089 are factors in PlAMV infection, whereas bZIP28 and bZIP60 are factors in TuMV infection. TGB3 and 6K2 transient expression in leave reveal that these alternative pathways induce BiPs expression. Finally, using dithiothreitol (DTT) and tauroursodeoxycholic acid (TUDCA) treatment, we demonstrated that the protein folding capacity significantly influences PlAMV accumulation. Together, these results indicate that multiple ER-to-nucleus signaling pathways are activated during virus infection and restrict virus accumulation through increasing protein folding capacity.Significance statementThe IRE1/bZIP60 pathway of unfolded protein response (UPR) is activated by potyviruses and potexviruses, limiting their infection, but the role of alternative UPR pathways is unknown. This study reveals the activation of multiple ER-to-nucleus signaling pathways by the Plantago asiatica mosaic virus and the Turnip mosaic virus. We identify additional signaling pathways serve to restrict virus accumulation through increased protein folding capacity.

Turnip mosaic virus, a virus for all seasons

“…The viral protein 6 K2 is responsible for the membrane proliferation taking place soon after TuMV cell infection (Grangeon et al, 2012). It has also been shown to activate alternative transcription pathways that result in the repression of local and systemic TuMV infection (Gayral et al, 2020). Other proteins, both viral and cellular are attracted to these viral replication structures to complete the replication process (Y.…”

“…The viral protein 6 K2 is responsible for the membrane proliferation taking place soon after TuMV cell infection (Grangeon et al, 2012). It has also been shown to activate alternative transcription pathways that result in the repression of local and systemic TuMV infection (Gayral et al, 2020). Other proteins, both viral and cellular are attracted to these viral replication structures to complete the replication process (Y. Li, Xiong, Bernards, & Wang, 2016; Movahed, Garcia Cabanillas, et al, 2019; Thivierge et al, 2008; Wu et al, 2020), although a thorough understanding of the components of the replication complexes is still far off.…”

Tobacco necrosis virus A overcomes local cell death response in Nicotiana tabacum

“…The unrestricted activity of erUPR, a consequence of viral replication and misfolded protein accumulation, may lead to HR‐associated cell death (Simoni et al, 2022; Verchot & Pajerowska‐Mukhtar, 2021). Two major UPR signalling pathways are activated by viral infection; one is mediated by the interaction of inositol‐requiring enzyme‐1 (IRE1), which mediates unconventional splicing of bZIP60 transcription factor mRNA, and the other by bZIP17 and bZIP28 (Gayral et al, 2020; Herath et al, 2020; Li et al, 2022; Zhang et al, 2015). UPR activation causes the up‐regulation of ER stress‐related genes encoding chaperones, proteases and proteins involved in detoxification pathways, including calreticulin (CRT) and protein disulphide isomerase (PDI) (Manghwar & Li, 2022).…”

Plantago asiatica mosaic virus: An emerging plant virus causing necrosis in lilies and a new model RNA virus for molecular research

“…Indeed, ER‐localized TGBp3 of PVX was shown to induce unfolded protein responses (UPR), enhancing protein‐folding capacity at ER, especially of the IRE1/bZIP60 pathway (Gaguancela et al, 2016). As well as the IRE1/bZIP60 pathway, the IRE1‐independent bZIP17 pathway functions to restrict early stages of PlAMV infection in Arabidopsis plants, indicating that the two arms of UPR signalling inhibit the accumulation of PlAMV (Gayral et al, 2020). Meanwhile, bZIP60 and bZIP28 induce genes that support PlAMV infection, suggesting that plants have intricate regulatory mechanisms of UPR on virus infection (Herath et al, 2020).…”