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. Arboviruses form episomal viral DNA fragments 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 analyze 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, but are ∼10-fold less abundant in all other mosquitoes 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 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 exits. Viral integrations are abundant in Ae. aegypti and Ae. albopictus, and represent a thus far unappreciated 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.
LIST OF ABBREVIATIONS
- DENV
- dengue viruses
- ZKV
- Zika virus
- CHIKV
- chikungunya virus
- VEE
- Venezuelan equine encephalitis
- EEE
- eastern equine encephalitis
- LACV
- La Crosse virus
- RVFV
- Rift Valley fever virus
- WNV
- West Nile virus
- siRNA
- small interfering RNA
- piRNA
- PIWI-interacting RNA
- EVEs
- Endogenous Viral Elements
- NIRVS
- Non-Retroviral Integrated RNA Viruses Sequences
- N
- Nucleoprotein
- G
- Glycoprotein
- L
- RNA-dependent RNA polymerase
- ORF
- Open Reading Frame
- IP
- immunoprecipitations
- LTR
- long terminal repeat (LTR) retrotransposons
- TE
- transposable elements
- ISV
- Insect Specific Virus
- PTS
- piRNA trigger sequence
- BWA
- Burrows-Wheeler Aligner
- ML
- Maximum likelihood
- Ct=
- cycle threshold
- RPKM
- Reads per kilobase per million mapped reads