Coordination between terminal variation of the viral genome and insect microRNAs regulates rice stripe virus replication in insect vectors

Maintenance of a balance between the levels of viral replication and selective pressure from the immune systems of insect vectors is one of the prerequisites for efficient transmission of insect-borne propagative phytoviruses. The mechanism regulating the adaptation of RNA viruses to insect vectors by genomic variation remains unknown. Our previous study demonstrated an extension of the 3'-untranslated terminal region (UTR) of two genomic segments of rice stripe virus (RSV). In the present study, a reverse genetic system for RSV in human cells and an insect vector, the small brown planthopper Laodelphax striatellus, was used to demonstrate that the 3'-terminal extensions suppressed viral replication in vector insects by inhibiting promoter activity due to structural interference with the panhandle structure formed by viral 3'- and 5'-UTRs. The extension sequence in the viral RNA1 segment was targeted by an endogenous insect microRNA, miR-263a, which decreased the inhibitory effect of the extension sequence on viral promoter activity. Surprisingly, the expression of miR-263a was negatively regulated by RSV infection. This elaborate coordination between terminal variation of the viral genome and endogenous insect microRNAs controls RSV replication in planthopper, thus reflecting a distinct strategy of adaptation of phytoviruses to insect vectors. Author summary Mutations frequently happen when insect-transmitted RNA viruses circulate between insect vectors and plant or mammalian hosts. However, the significance of these mutations for viral fitness in the two distinct organisms is poorly understood. We discovered that a high proportion of rice stripe virus (RSV) had terminally extended genomes when the virus infected insect vectors. In the present study, we found that the extension sequence suppressed viral replication in insect vectors by impairing a special structure formed by the two ends of the viral genomes. An endogenous insect small RNA was able to bind the extension sequence to relieve the inhibitory effect. However, the expression of this small RNA was reduced in the presence of RSV to ultimately maintain the inhibitory effect of the extension sequence. This elaborate coordination between virus and vector enables a limited level of RSV replication that does not produce serious damage to vectors, thus reflecting a distinct strategy of adaptation of insect-transmitted plant viruses.

Automated summary

Maintenance of a balance between viral replication and selective pressure from insect vectors' immune systems is crucial for efficient transmission of insect-borne phytoviruses, with the mechanisms of RNA virus adaptation to insect vectors remaining largely unknown. In this study, researchers found that terminal extensions in the genome of rice stripe virus (RSV) can suppress viral replication in insect vectors by interfering with a key structure, and endogenous insect microRNA can relieve this inhibitory effect. However, RSV infection negatively regulates the expression of this microRNA, highlighting an intricate coordination between viral genome variation and insect microRNAs in controlling RSV replication in planthopper vectors.