Arbovirus persistence in mosquitoes is characterized by translation repression of viral RNAs

Abstract Arboviruses induce acute lytic infection in human cells but establish persistent infection in their mosquito vectors, a viral strategy that is essential for sustained viral transmission. How mosquito cells maintain continuous production of viral progeny without compromising host cell viability remains a fundamental unresolved question. Because arbovirus replication in human cells relies on viral takeover of the host translational machinery, we investigated how translation is regulated during persistent infection in mosquito cells using chikungunya virus (CHIKV) as a model. A temporal analysis of viral RNA translation in RNAi-competent and RNAi-deficient Aedes albopictus cells revealed that persistence was associated with reduced viral protein production resulting from translation repression of viral RNAs. Subcellular localization analyses of the viral protein nsP2 and LC–MS/MS analyses of host tRNAs showed that, in contrast to human cells, CHIKV infection in mosquito cells neither induced nuclear relocalization of viral nsP2 to induce global host mRNA depletion, nor reshaped the tRNA modification landscape to compensate for the suboptimal codon usage of viral RNAs. Together, our results indicate that persistent infection in mosquito cells is characterized by a balanced host–virus translational state, in which limited viral translation is maintained while viral takeover of the host translational machinery is avoided. Notably, translation repression of viral RNAs was also observed during Zika virus (ZIKV) infection, suggesting that this mechanism may represent a general RNAi-independent feature of arbovirus persistence in mosquito cells.