Open AccessDefective viral genomes from chikungunya virus are broad-spectrum antivirals and prevent virus dissemination in mosquitoes
Author(s) -
Laura Levi,
Veronica V. Rezelj,
Annabelle Henrion-Lacritick,
Diana Erazo,
Jérémy Boussier,
Thomas Vallet,
Veronika Bernhauerová,
Yasutsugu Suzuki,
Lucía Carrau,
James Weger-Lucarelli,
Maria-Carla Saleh,
Marco Vignuzzi
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009110
Subject(s) - chikungunya , virology , alphavirus , biology , virus , aedes aegypti , viral replication , sindbis virus , aedes , togaviridae , genome , rna virus , zika virus , vector (molecular biology) , rna , dengue fever , genetics , gene , recombinant dna , botany , larva
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 .