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Defective viral genomes as therapeutic interfering particles against flavivirus infection in mammalian and mosquito hosts

Rezelj, Veronica V ; Carrau, Lucía ; Merwaiss, Fernando ; Levi, Laura I ; Erazo, Diana ; Tran, Quang Dinh ; Henrion-Lacritick, Annabelle ; Gausson, Valérie ; Suzuki, Yasutsugu ; Shengjuler, Djoshkun ; Meyer, Bjoern ; Vallet, Thomas ; Weger-Lucarelli, James ; Bernhauerová, Veronika ; Titievsky, Avi ; Sharov, Vadim ; Pietropaoli, Stefano ; Diaz-Salinas, Marco A ; Legros, Vincent ; Pardigon, Nathalie ; Barba-Spaeth, Giovanna ; Brodsky, Leonid ; Saleh, Maria-Carla ; Vignuzzi, Marco

Nature communications, 2021-04, Vol.12 (1), p.2290-2290, Article 2290 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Defective viral genomes as therapeutic interfering particles against flavivirus infection in mammalian and mosquito hosts
Autor: Rezelj, Veronica V ; Carrau, Lucía ; Merwaiss, Fernando ; Levi, Laura I ; Erazo, Diana ; Tran, Quang Dinh ; Henrion-Lacritick, Annabelle ; Gausson, Valérie ; Suzuki, Yasutsugu ; Shengjuler, Djoshkun ; Meyer, Bjoern ; Vallet, Thomas ; Weger-Lucarelli, James ; Bernhauerová, Veronika ; Titievsky, Avi ; Sharov, Vadim ; Pietropaoli, Stefano ; Diaz-Salinas, Marco A ; Legros, Vincent ; Pardigon, Nathalie ; Barba-Spaeth, Giovanna ; Brodsky, Leonid ; Saleh, Maria-Carla ; Vignuzzi, Marco
Assuntos: Aedes ; Aedes - drug effects ; Aedes - virology ; Animals ; Antiviral activity ; Antiviral Agents ; Antiviral Agents - administration & dosage ; Chemical compounds ; Chlorocebus aethiops ; Computational Biology ; Computer applications ; Defective Viruses ; Defective Viruses - genetics ; Directed Molecular Evolution ; Disease control ; Disease Models, Animal ; Disease transmission ; Evolution ; Female ; Fitness ; Genetic Fitness ; Genome, Viral ; Genome, Viral - genetics ; Genomes ; HEK293 Cells ; Humans ; Infections ; Life Sciences ; Mammals ; Mice ; Microbiology and Parasitology ; Mosquito Control ; Mosquito Control - methods ; Mosquito Vectors ; Mosquito Vectors - drug effects ; Mosquito Vectors - virology ; Mosquitoes ; Open Reading Frames ; Open Reading Frames - genetics ; Pharmacology ; Public health ; RNA, Viral ; RNA, Viral - genetics ; Structural proteins ; Vector-borne diseases ; Vero Cells ; Virology ; Viruses ; Zika Virus ; Zika Virus - genetics ; Zika Virus Infection ; Zika Virus Infection - drug therapy ; Zika Virus Infection - transmission ; Zika Virus Infection - virology
É parte de: Nature communications, 2021-04, Vol.12 (1), p.2290-2290, Article 2290
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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PMCID: PMC8052367
Descrição: Arthropod-borne viruses pose a major threat to global public health. Thus, innovative strategies for their control and prevention are urgently needed. Here, we exploit the natural capacity of viruses to generate defective viral genomes (DVGs) to their detriment. While DVGs have been described for most viruses, identifying which, if any, can be used as therapeutic agents remains a challenge. We present a combined experimental evolution and computational approach to triage DVG sequence space and pinpoint the fittest deletions, using Zika virus as an arbovirus model. This approach identifies fit DVGs that optimally interfere with wild-type virus infection. We show that the most fit DVGs conserve the open reading frame to maintain the translation of the remaining non-structural proteins, a characteristic that is fundamental across the flavivirus genus. Finally, we demonstrate that the high fitness DVG is antiviral in vivo both in the mammalian host and the mosquito vector, reducing transmission in the latter by up to 90%. Our approach establishes the method to interrogate the DVG fitness landscape, and enables the systematic identification of DVGs that show promise as human therapeutics and vector control strategies to mitigate arbovirus transmission and disease.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Defective viral genomes as therapeutic interfering particles against flavivirus infection in mammalian and mosquito hosts

England: Nature Publishing Group

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