The JAK-STAT pathway promotes persistent viral infection by activating apoptosis in insect vectors

Author summaryThe Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway acts as an innate antiviral immunity in mammals, while its role in the persistent transmission of plant viruses by insect vectors remains largely unknown. In this study, we reported that plant viral infection activated the JAK-STAT pathway and this pathway regulated apoptosis to benefit virus accumulation in the insect vector. This is a new regulatory mechanism of virus-induced apoptosis for persistent viral infection. Moreover, our new findings greatly expand our knowledge on the complex crosstalk between JAK-STAT and other pathways to facilitate persistent virus transmission in their insect vectors. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved signaling pathway that can regulate various biological processes. However, the role of JAK-STAT pathway in the persistent viral infection in insect vectors has rarely been investigated. Here, using a system that comprised two different plant viruses, Rice stripe virus (RSV) and Rice black-streaked dwarf virus (RBSDV), as well as their insect vector small brown planthopper, we elucidated the regulatory mechanism of JAK-STAT pathway in persistent viral infection. Both RSV and RBSDV infection activated the JAK-STAT pathway and promoted the accumulation of suppressor of cytokine signaling 5 (SOCS5), an E3 ubiquitin ligase regulated by the transcription factor STAT5B. Interestingly, the virus-induced SOCS5 directly interacted with the anti-apoptotic B-cell lymphoma-2 (BCL2) to accelerate the BCL2 degradation through the 26S proteasome pathway. As a result, the activation of apoptosis facilitated persistent viral infection in their vector. Furthermore, STAT5B activation promoted virus amplification, whereas STAT5B suppression inhibited apoptosis and reduced virus accumulation. In summary, our results reveal that virus-induced JAK-STAT pathway regulates apoptosis to promote viral infection, and uncover a new regulatory mechanism of the JAK-STAT pathway in the persistent plant virus transmission by arthropod vectors.