Proteolysis of host DEAD-box RNA helicase by potyviral proteases activates plant immunity

The precise mechanisms by which plant viral proteases interact with and cleave host proteins, thereby participating in virus-host interactions, are not well understood. Potyviruses, the largest group of known plant-infecting RNA viruses, are known to rely on the nuclear inclusion protease a (NIa-Pro) for the processing of viral polyproteins. Here, we demonstrate that the proteolytic activity of NIa-Pro from potyvirus turnip mosaic virus (TuMV) is indispensable for inducing hypersensitive cell death in Nicotiana benthamiana. NIa-Pro targets and degrades the host DEAD-box protein 5 (DBP5) via a specific cleavage motif, which initiates host cell death. Both the silencing of DBP5 and the overexpression of NIa-Pro lead to an increased frequency of stop codon readthrough, which could be potentially harmful to the host, as it may result in the production of aberrant proteins. Unlike the NIa-Pro of most other potyviruses, the NIa-Pro of tobacco etch virus can also degrade DBP5 and trigger cell death, in both pepper and N. benthamiana. Furthermore, we discovered that the TuMV-encoded nuclear inclusion b can counteract NIa-Pro-induced cell death by co-opting DBP5. These findings unveil hitherto uncharacterized roles for plant virus proteases in cleaving host proteins and highlight the role of host DBP5 in modulating plant immunity.