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

• DOI: 10.1371/journal.ppat.1009110
• Publication Date: 2021-02-08T18:42:26Z
• Authors: Laura I. Levi; Veronica V. Rezelj; Annabelle Henrion...; Diana Erazo; J Boussier; Thomas Vallet; Veronika Bernhaue...; Yasutsugu Suzuki; Lucia Carrau; James Weger-Lucar...; Maria-Carla Saleh; Marco Vignuzzi
• Keywords: 0303 health sciences; QH301-705.5; [SDV]Life Sciences [q-bio]; Defective Viruses; Genome, Viral; Mosquito Vectors; RC581-607; Virus Replication; Antiviral Agents; 3. Good health; 03 medical and health sciences; [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology; Aedes; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; Animals; Chikungunya Fever; Humans; Immunologic diseases. Allergy; Biology (General); Chikungunya virus; Research Article

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.