ABSTRACT
Rift Valley fever virus (RVFV) is an emerging, mosquito-borne, zoonotic pathogen with recurrent outbreaks taking a considerable toll in human deaths in many African countries, for which no effective treatment is available. In cell culture studies and with laboratory animal models, the nucleoside analogue favipiravir (T-705) has demonstrated great potential for the treatment of several seasonal, chronic, and emerging RNA virus infections in humans, suggesting applicability to control some viral outbreaks. Treatment with favipiravir was shown to reduce the infectivity of Rift Valley fever virus both in cell cultures and in experimental animal models, but the mechanism of this protective effect is not understood. In this work, we show that favipiravir at concentrations well below the toxicity threshold estimated for cells is able to extinguish RVFV from infected cell cultures. Nucleotide sequence analysis has documented RVFV mutagenesis associated with virus extinction, with a significant increase in G to A and C to U transition frequencies and a decrease of specific infectivity, hallmarks of lethal mutagenesis.
FOOTNOTES
- Received 5 April 2019.
- Returned for modification 23 April 2019.
- Accepted 8 May 2019.
- Accepted manuscript posted online 13 May 2019.
Supplemental material for this article may be found at https://doi.org/10.1128/AAC.00669-19.
- Copyright © 2019 Borrego et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
