Endogenous retroviral elements are known to contribute to host immunity and restriction of viral infections. Potential functions of endogenous viral elements (EVEs) derived from other viruses than retroviruses are less clear. Suzuki, Baidaliuk et al. now show that an EVE can reduce infection levels of its cognate virus in Aedes aegypti mosquitoes.
Mosquitoes harbour hundreds of EVEs derived from insect-specific viruses, and previous in vitro work has suggested that these EVEs might have a role in restricting infection with matching viruses through the P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway. These small RNAs can be derived from EVEs, and if their sequence matches an exogenous virus and they are in an antisense orientation they can target the viral RNA. Furthermore, in a so-called ‘ping-pong’ cycle, primary piRNAs can cleave complementary RNAs, leading to the generation of secondary piRNAs from the cleavage products, which in turn process piRNA precursor transcripts and thus generate more primary piRNAs.
The authors had previously isolated cell-fusing agent virus (CFAV) from wild Ae. aegypti in Thailand. In the current study, they mined mosquito genomes for potential EVEs that match the viral sequence and identified two putative EVEs. Indeed, when they checked an outbred colony of mosquitoes derived from wild Ae. aegypti captured in Thailand, many individuals harboured those EVEs, and those that did also produced EVE-derived primary piRNAs.
Part of the mosquito colony is naturally infected with CFAV, and infected individuals had both EVE-derived primary piRNAs and virus-derived secondary piRNAs, showing that ping-pong amplification is active. Furthermore, a mosquito line in which the EVE was knocked out with CRISPR–Cas showed a lack of virus-derived secondary piRNAs. When infected, the engineered mosquitoes did not show activation of ping-pong amplification and they had higher viral loads, in particular in the ovaries, 7 days after experimental infection with CFAV.
“the engineered mosquitoes did not show activation of ping-pong amplification and they had higher viral loads”
In summary, the study shows that EVEs can have antiviral effects in mosquitoes, potentially to reduce vertical viral transmission to the offspring.
Suzuki, Y., Baidaliuk, A. et al. Non-retroviral endogenous viral element limits cognate virus replication in Aedes aegypti ovaries. Curr. Biol. https://doi.org/10.1016/j.cub.2020.06.057 (2020)
Perlmutter, J. I. & Bordenstein, S. R. Microorganisms in the reproductive tissues of arthropods. Nat. Rev. Microbiol. 18, 97–111 (2020)
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Hofer, U. Antiviral ping-pong in mosquitoes. Nat Rev Microbiol 18, 542–543 (2020). https://doi.org/10.1038/s41579-020-0429-5