Zhao Wan, Wang Wei, Xiao Yan, Cui Feng
State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, 100049, China.
State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Insect Biochem Mol Biol. 2023 Jan;152:103894. doi: 10.1016/j.ibmb.2022.103894. Epub 2022 Dec 16.
The c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in viral infection in host cells. In addition to triggering immune reactions against pathogens, the JNK signaling pathway has also been found to benefit viral infection. Our previous work showed that JNK activation facilitated rice stripe virus (RSV) accumulation in the insect vector small brown planthopper, but the underlying mechanisms remain elusive. Here, we revealed a link between JNK activation and the transcriptional upregulation of the plasma membrane protein flotillin 2, which mediates RSV cell entry. c-Jun, a downstream substrate of JNKs, was identified as a transcription factor that targets the promoter of flotillin 2 at three binding sites. Phosphorylated c-Jun, especially at the serine 63 site, promoted the transcriptional activity of c-Jun on flotillin 2. JNK activation or inhibition affected c-Jun phosphorylation status and flotillin 2 expression. In the midguts of planthoppers, RSV infection significantly increased flotillin 2 expression and the phosphorylation level of JNKs and c-Jun. Manipulation of JNK status impacted viral acquisition in midgut cells. These findings reveal a new regulatory mechanism of the JNK signaling pathway and shed light on the virus-supportive effect of this pathway.
c-Jun氨基末端激酶（JNK）信号通路在宿主细胞的病毒感染中起关键作用。除了触发针对病原体的免疫反应外，JNK信号通路也被发现有利于病毒感染。我们之前的研究表明，JNK激活促进了水稻条纹病毒（RSV）在昆虫介体灰飞虱中的积累，但其潜在机制仍不清楚。在此，我们揭示了JNK激活与质膜蛋白flotillin 2转录上调之间的联系，flotillin 2介导RSV进入细胞。JNK的下游底物c-Jun被鉴定为一种转录因子，它在三个结合位点靶向flotillin 2的启动子。磷酸化的c-Jun，尤其是丝氨酸63位点的磷酸化，促进了c-Jun对flotillin 2的转录活性。JNK的激活或抑制影响c-Jun的磷酸化状态和flotillin 2的表达。在灰飞虱的中肠中，RSV感染显著增加了flotillin 2的表达以及JNK和c-Jun的磷酸化水平。操纵JNK状态会影响中肠细胞中的病毒获取。这些发现揭示了JNK信号通路的一种新的调控机制，并阐明了该通路对病毒的支持作用。
