Wang Hui, Zhang Jieting, Liu Runfa, Li You, Du Yu, Wei Taiyun
State Key Laboratory of Agricultural and Forestry Biosecurity, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.
PLoS Pathog. 2025 May 29;21(5):e1013178. doi: 10.1371/journal.ppat.1013178. eCollection 2025 May.
Co-infection with symbiotic viruses and arboviruses with synergistic effects in insect vectors are common in nature, but the underlying mechanism remains elusive. Here, we identify a novel symbiotic virus, leafhopper Recilia dorsalis bunyavirus (RdBV), which enhances the transmission efficiency of cytorhabdovirus rice stripe mosaic virus (RSMV, a plant rhabdovirus) in field. RSMV infection activates the expression of R. dorsalis E3 ubiquitin ligase Seven in absentia (RdSina), while RdBV infection suppresses its expression. We show that RdSina directly targets and mediates the degradation of RSMV phosphoprotein (P), thereby attenuating the formation of P-induced viroplasm that are crucial for viral replication. RdSina interacts with nonstructural protein NSs2 of RdBV but does not mediate its ubiquitination. However, NSs2 competes with RSMV P for binding to RdSina, thus neutralizing RdSina's ability in mediating P degradation. Furthermore, we find that the MYC transcription factor binds to the promoter sequences of RdSina, activating its transcription. However, NSs2 also directly binds to the same promoter sequences of RdSina and competitively suppresses MYC-activated RdSina transcription. Together, NSs2 obstructs the function of RdSina in mediating P degradation, ultimately promoting RSMV propagation in co-infected vectors. These findings elucidate how insect symbiotic viruses negatively regulate E3 ubiquitin ligases to benefit arbovirus transmission by co-infected insect vectors, which potentially is a common phenomenon in nature.
共生病毒与虫媒病毒在昆虫媒介中共同感染并产生协同效应在自然界中很常见，但其潜在机制仍不清楚。在这里，我们鉴定出一种新型共生病毒，叶蝉背突布尼亚病毒（RdBV），它在田间提高了细胞质弹状病毒水稻条纹花叶病毒（RSMV，一种植物弹状病毒）的传播效率。RSMV感染激活了背突叶蝉E3泛素连接酶Seven in absentia（RdSina）的表达，而RdBV感染则抑制其表达。我们发现RdSina直接靶向并介导RSMV磷蛋白（P）的降解，从而减弱对病毒复制至关重要的P诱导的病毒质的形成。RdSina与RdBV的非结构蛋白NSs2相互作用，但不介导其泛素化。然而，NSs2与RSMV P竞争与RdSina的结合，从而中和RdSina介导P降解的能力。此外，我们发现MYC转录因子与RdSina的启动子序列结合，激活其转录。然而，NSs2也直接与RdSina的相同启动子序列结合，并竞争性抑制MYC激活的RdSina转录。总之，NSs2阻碍了RdSina介导P降解的功能，最终促进了RSMV在共感染媒介中的传播。这些发现阐明了昆虫共生病毒如何通过负调控E3泛素连接酶来促进共感染昆虫媒介传播虫媒病毒，这在自然界中可能是一种常见现象。
