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

ABSTRACT: 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 cha

SUBMITTER: Rezelj VV 

PROVIDER: S-EPMC8052367 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature