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

Wan Zhao,Wei Wang,Le Kang,Jinting Yu,Feng Jiang,Feng Cui,Aiming Wang

doi:10.1371/journal.ppat.1009424

Abstract

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.

Highlights

Insect-borne propagative phytoviruses and arboviruses usually induce serious or fatal diseases in plant and mammalian hosts in contrast to the asymptomatic infection in insect vectors [1,2]
We discovered that a high proportion of rice stripe virus (RSV) had terminally extended genomes when the virus infected insect vectors
We found that the extension sequence suppressed viral replication in insect vectors by impairing a special structure

Summary

Introduction

Insect-borne propagative phytoviruses and arboviruses usually induce serious or fatal diseases in plant and mammalian hosts in contrast to the asymptomatic infection in insect vectors [1,2]. Genetic variation is frequently observed in insect-borne RNA viruses during viral circulation in two distinct organisms. The mechanism of the regulation of adaptation of a virus to insect vectors by variations in the UTRs is currently unknown. The UTRs of single-stranded RNA viruses play the key roles in viral replication and gene transcription. The 3’- and 5’-UTRs of negative-strand RNA viruses form a panhandle structure via distal complementary 15–19 nucleotides (nt) to provide a binding site for viral RNAdependent RNA polymerase (RdRp) [5,6]. Mutations in the 3’UTRs usually negatively impact viral replication, transcription, or translation [7]. Endogenous microRNAs (miRNAs) of the host cells have been frequently reported to target the 3’-UTRs of RNA viruses to regulate viral replication [8,9]

Objectives

Methods

Results

Discussion

Conclusion