Levi, L.I; Rezelj, V.V; Henrion-Lacritik, A; Erazo, D; Boussier, J; Vallet, T; Bernhauerová, V; Suzuki, Y; Carrau, L; Weger-Lucarelli, J; Saleh, M.C; Vignuzzi, M
PLoS pathogens 02/12/2020
PMID: In press
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 caused millions of human cases in the last 15 years. Here, we describe the DVGs arising during chikungunya virus 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 chikungunya virus replication both in mammalian and mosquito cells. We further demonstrated that some DVGs present broad-spectrum activity, inhibiting other chikungunya virus strains and other alphaviruses. Finally, we showed that pre-treating Aedes aegypti with DVGs prevents viral dissemination in vivo, encouraging the development of a new kind of vector control strategy.