RNAi Regulator C3PO Promotes Arbovirus Infection in Insect Vectors

Numerous plant and human viruses depend on arthropods for their transmission. RNA interference (RNAi) constitutes a pivotal antiviral immune system in arthropods. Component 3 promoter of RISC (C3PO) complex plays an important regulatory role in small RNA production of the RNAi pathway. However, how C3PO affects viral infection in arthropod vectors remains elusive. Here, using the system of rice stripe virus (RSV) and its insect vector small brown planthopper, we found that C3PO facilitates RSV replication in insect vectors. C3PO directly degrades precursors of miRNAs, especially miR-971-3p. The RNA-dependent RNA polymerase (RdRp) of RSV synergistically cooperates with C3PO to degrade miR-971-3p precursor. The reduction of miR-971-3p elevates the expression of target gene NHL repeat-containing protein 2 (NHLRC2), which scavenges reactive oxygen species, thereby facilitating viral replication. Similar function of C3PO is elucidated in mosquitoes during the infection of sindbis virus, indicating the conservation of insect C3PO taking part in arbovirus infection. Our study extends the understanding of C3PO in insect vectors and offers the potential of C3PO as target for reducing arbovirus transmission.