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bioRxiv · 10.1101/124032

Uncovering The Repertoire Of Endogenous Flaviviral Elements In Aedes Mosquito Genomes

Suzuki, Y.·Frangeul, L.·Dickson, L. B.·Blanc, H.·Verdier, Y.·Vinh, J.·Lambrechts, L.·Saleh, M.-C.
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Abstract

Endogenous viral elements derived from non-retroviral RNA viruses were described in various animal genomes. Whether they have a biological function such as host immune protection against related viruses is a field of intense study. Here, we investigated the repertoire of endogenous flaviviral elements (EFVEs) in Aedes mosquitoes, the vectors of arboviruses such as dengue and chikungunya viruses. Previous studies identified three EFVEs from Ae. albopictus and one from Ae. aegypti cell lines. However, in-depth characterization of EFVEs in wild-type mosquito populations and individuals in vivo has not been performed. We detected the full-length DNA sequence of the previously described EFVEs and their respective transcripts in several Ae. albopictus and Ae. aegypti populations from geographically distinct areas. However, EFVE-derived proteins were not detected by mass spectrometry. Using deep sequencing, we detected the production of piRNA-like small RNAs in antisense orientation, targeting the EFVEs and their flanking regions in vivo. The EFVEs were integrated in repetitive regions of the mosquito genomes, and their flanking sequences varied among mosquito populations from different geographical regions. We bioinformatically predicted several new EFVEs from a Vietnamese Ae. albopictus population and observed variation in the occurrence of those elements among mosquito populations. Phylogenetic analysis of an Ae. aegypti EFVE suggested that it integrated prior to the global expansion of the species and subsequently diverged among and within populations. Together, this study revealed substantial structural and nucleotide diversity of flaviviral integrations in Aedes genomes. Unraveling this diversity will help to elucidate the potential biological function of these EFVEs.\n\nImportanceEndogenous viral elements (EVEs) are whole or partial viral sequences integrated in host genomes. Interestingly, some EVEs have important functions for host fitness and antiviral defense. Because mosquitoes also have EVEs in their genomes, we decided to thoroughly characterized them to lay the foundation of the potential use of these EVEs to manipulate the mosquito antiviral response. Here, we focused on EVEs related to the Flavivirus genus, to which dengue and Zika viruses belong, in Aedes mosquito individuals from geographically distinct areas. We showed the existence in vivo of flaviviral EVEs previously identified in mosquito cell lines and we detected new ones. We showed that EVEs have evolved differently in each mosquito population. They produced transcripts and small RNAs, but not proteins, suggesting a function at the RNA level. Our study uncovers the diverse repertoire of flaviviral EVEs in Aedes mosquito populations and suggests a role in the host antiviral system.

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Suzuki, Y., Frangeul, L., Dickson, L. B., Blanc, H., Verdier, Y., Vinh, J., Lambrechts, L., Saleh, M.-C.. 2017-04-04. Uncovering The Repertoire Of Endogenous Flaviviral Elements In Aedes Mosquito Genomes. https://doi.org/10.1101/124032

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