Comparative genomics shows that viral integrations are abundant and express piRNAs in the arboviral vectors Aedes aegypti and Aedes albopictus

Abstract

Background: Arthropod-borne viruses (arboviruses) transmitted by mosquito vectors cause many important emerging or resurging infectious diseases in humans including dengue, chikungunya and Zika. Understanding the co-evolutionary processes among viruses and vectors is essential for the development of novel transmission-blocking strategies. Episomal viral DNA fragments are produced from arboviral RNA upon infection of mosquito cells and adults. Additionally, sequences from insect-specific viruses and arboviruses have been found integrated into mosquito genomes. Results: We used a bioinformatic approach to analyse the presence, abundance, distribution, and transcriptional activity of integrations from 425 non-retroviral viruses, including 133 arboviruses, across the presently available 22 mosquito genome sequences. Large differences in abundance and types of viral integrations were observed in mosquito species from the same region. Viral integrations are unexpectedly abundant in the arboviral vector species Aedes aegypti and Ae. albopictus, in which they are approximately ~10-fold more abundant than in other mosquito species analysed. Additionally, viral integrations are enriched in piRNA clusters of both the Ae. aegypti and Ae. albopictus genomes and, accordingly, they express piRNAs, but not siRNAs. Conclusions: Differences in the number of viral integrations in the genomes of mosquito species from the same geographic area support the conclusion that integrations of viral sequences is not dependent on viral exposure, but that lineage-specific interactions exist. Viral integrations are abundant in Ae. aegypti and Ae. albopictus, and represent a thus far underappreciated component of their genomes. Additionally, the genome locations of viral integrations and their production of piRNAs indicate a functional link between viral integrations and the piRNA pathway. These results greatly expand the breadth and complexity of small RNA-mediated regulation and suggest a role for viral integrations in antiviral defense in these two mosquito species.