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

Abstract

BackgroundArthropod-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.ResultsWe 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.ConclusionsDifferences 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3903-3) contains supplementary material, which is available to authorized users.

The Diversity, Structure, and Function of Heritable Adaptive Immunity Sequences in the Aedes aegypti Genome

“…An association between LTR Ty3/gypsy elements and integrated viral sequence has also been observed previously in plants (and recently in adult mosquitoes) [17, 19, 20], suggesting a conserved mechanism for the acquisition and endogenization of viral sequences. We also observed an association between LTR and viral families.…”

“…aegypti and Ae. albopictus (Figure 1a) [17], may represent a factor contributing to inherent differences in vector competence across many different scales. Indeed, the EVEome of wild mosquito populations appears to be in rapid flux [34].…”

“…Furthermore, both involve endogenization of viral sequences, potentially providing protection against infection across generations. The extent of conservation of this pathway across Eukarya is not yet clear, however recent publications have highlighted the endogenization of genetic material from non-retroviral RNA viruses into the genome of many different host species [5, 17, 36]. The antiviral activity of these sequences has not been established, however a subset of EVEs found in mammalian systems appear to be under purifying selection, suggesting some potential benefit to the host [22].…”

Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements

“…13), a feature reminiscent of the somatic piRNAs present in Drosophila follicle cells 4,5 . Despite removing sequencing reads that map to the reference genome, we cannot exclude the possibility that these piRNAs come from viruses integrated in the host genome 29 . Together these results suggest that although some viruses may be targeted by somatic piRNAs, siRNAs likely remain the primary antiviral defence against most viruses across the arthropods.…”

African swine fever virus-like integrated elements in a soft tick genome – an ancient virus vector arms race?

“…However, protection against homologous viruses was demonstrated after integration of retroviral-elements in mice, sheep (41) and bats (27), and is also discussed for EBLN-elements (27,30). Furthermore, transcriptional activity of EVEs and protection against viral infection was demonstrated to occur in crustaceans (29,31,32) and mosquitoes (42,43).…”