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Defective viral genomes from chikungunya virus are broad-spectrum antivirals and prevent virus dissemination in mosquitoes

Abstract : Defective viral genomes (DVGs) are truncated and/or rearranged viral genomes produced during virus replication. Described in many RNA virus families, some of them have interfering activity on their parental virus and/or strong immunostimulatory potential, and are being considered in antiviral approaches. Chikungunya virus (CHIKV) is an alphavirus transmitted by Aedes spp . that infected millions of humans in the last 15 years. Here, we describe the DVGs arising during CHIKV infection in vitro in mammalian and mosquito cells, and in vivo in experimentally infected Aedes aegypti mosquitoes. We combined experimental and computational approaches to select DVG candidates most likely to have inhibitory activity and showed that, indeed, they strongly interfere with CHIKV replication both in mammalian and mosquito cells. We further demonstrated that some DVGs present broad-spectrum activity, inhibiting several CHIKV strains and other alphaviruses. Finally, we showed that pre-treating Aedes aegypti with DVGs prevented viral dissemination in vivo .
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03260576
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Submitted on : Tuesday, June 15, 2021 - 9:54:11 AM
Last modification on : Tuesday, October 19, 2021 - 10:29:30 PM
Long-term archiving on: : Thursday, September 16, 2021 - 6:16:26 PM

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Laura Levi, Veronica Rezelj, Annabelle Henrion-Lacritick, Diana Erazo, J Boussier, et al.. Defective viral genomes from chikungunya virus are broad-spectrum antivirals and prevent virus dissemination in mosquitoes. PLoS Pathogens, Public Library of Science, 2021, 17 (2), pp.e1009110. ⟨10.1371/journal.ppat.1009110⟩. ⟨pasteur-03260576⟩

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