scholarly journals Extinction of West Nile Virus by Favipiravir through Lethal Mutagenesis

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Estela Escribano-Romero ◽  
Nereida Jiménez de Oya ◽  
Esteban Domingo ◽  
Juan Carlos Saiz
Keyword(s):  
West Nile Virus ◽  
Mutation Frequency ◽  
Ebola Virus ◽  
Rna Viruses ◽  
Lethal Dose ◽  
Antiviral Agent ◽  
West Nile ◽  
Lethal Mutagenesis ◽  
Mutant Spectrum

ABSTRACT Favipiravir is an antiviral agent effective against several RNA viruses. The drug has been shown to protect mice against experimental infection with a lethal dose of West Nile virus (WNV), a mosquito-borne flavivirus responsible for outbreaks of meningitis and encephalitis for which no antiviral therapy has been licensed; however, the mechanism of action of the drug is still not well understood. Here, we describe the potent in vitro antiviral activity of favipiravir against WNV, showing that it decreases virus-specific infectivity and drives the virus to extinction. Two passages of WNV in the presence of 1 mM favipiravir—a concentration that is more than 10-fold lower than its 50% cytotoxic concentration (CC50)—resulted in a significant increase in mutation frequency in the mutant spectrum and in a bias toward A→G and G→A transitions relative to the population passaged in the absence of the drug. These data, together with the fact that the drug is already licensed in Japan against influenza virus and in a clinical trial against Ebola virus, point to favipiravir as a promising antiviral agent to fight medically relevant flaviviral infections, such as that caused by WNV.

scholarly journals Characterization of mosquito-adapted West Nile virus

2008 ◽  
Vol 89 (7) ◽  
pp. 1633-1642 ◽  
Author(s):  
Alexander T. Ciota ◽  
Amy O. Lovelace ◽  
Yongqing Jia ◽  
Lauren J. Davis ◽  
David S. Young ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Nucleotide Substitutions ◽  
West Nile ◽  
Mutant Spectrum ◽  
Underlying Mechanisms ◽  
Virus Adaptation ◽  
Cell Spread

West Nile virus (WNV), a mosquito-borne flavivirus, has significantly expanded its geographical and host range since its 1999 introduction into North America. The underlying mechanisms of evolution of WNV and other arboviruses are still poorly understood. Studies evaluating virus adaptation and fitness in relevant in vivo systems are largely lacking. In order to evaluate the capacity for host-specific adaptation and the genetic correlates of adaptation in vivo, this study measured phenotypic and genotypic changes in WNV resulting from passage in Culex pipiens mosquitoes. An increase in replicative ability of WNV in C. pipiens was attained for the two lineages of WNV tested. This adaptation for replication in mosquitoes did not result in a replicative cost in chickens, but did decrease cell-to-cell spread of virus in vertebrate cell culture. Genetic analyses of one mosquito-adapted lineage revealed a total of nine consensus nucleotide substitutions with no accumulation of a significant mutant spectrum. These results differed significantly from previous in vitro studies. When St Louis encephalitis virus (SLEV), a closely related flavivirus, was passaged in C. pipiens, moderately attenuated growth in C. pipiens was observed for two lineages tested. These results suggest that significant differences in the capacity for mosquito adaptation may exist between WNV and SLEV, and demonstrate that further comparative studies in relevant in vivo systems will help elucidate the still largely unknown mechanisms of arboviral adaptation in ecologically relevant hosts.

scholarly journals The recently identified flavivirus Bamaga virus is transmitted horizontally by Culex mosquitoes and interferes with West Nile virus replication in vitro and transmission in vivo

2018 ◽  
Vol 12 (10) ◽  
pp. e0006886 ◽  
Author(s):  
Agathe M. G. Colmant ◽  
Sonja Hall-Mendelin ◽  
Scott A. Ritchie ◽  
Helle Bielefeldt-Ohmann ◽  
Jessica J. Harrison ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Virus Replication ◽  
West Nile ◽  
Culex Mosquitoes

scholarly journals Human Monoclonal Fab Antibodies Against West Nile Virus and its Neutralizing Activity Analyzed in Vitro and in Vivo

2009 ◽  
Vol 01 (01) ◽  
pp. 036-042 ◽  
Author(s):  
Tao Duan ◽  
Monique Ferguson ◽  
Lintian Yuan ◽  
Fangling Xu ◽  
Guangyu Li
Keyword(s):  
West Nile Virus ◽  
West Nile ◽  
Neutralizing Activity

scholarly journals Transstadial Transmission and Replication Kinetics of West Nile Virus Lineage 1 in Laboratory Reared Ixodes ricinus Ticks

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 780
Author(s):  
Cristian Răileanu ◽  
Oliver Tauchmann ◽  
Ana Vasić ◽  
Ulrike Neumann ◽  
Birke Andrea Tews ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Ixodes Ricinus ◽  
Tick Species ◽  
Vector Competence ◽  
Virus Transmission ◽  
Viral Agent ◽  
West Nile ◽  
Transstadial Transmission ◽  
Kinetics Of

West Nile virus (WNV) is a mosquito-borne agent that has also been isolated from several tick species. Vector competence of Ixodes ricinus, one of the most common tick species in Europe, has been poorly investigated for WNV to date. As such, to evaluate the vector competence, laboratory reared Ixodes ricinus nymphs were in vitro fed with WNV lineage 1 infectious blood, allowed to molt, and the resulting females artificially fed to study the virus transmission. Furthermore, we studied the kinetics of WNV replication in ticks after infecting nymphs using an automatic injector. Active replication of WNV was detected in injected nymphs from day 7 post-infection until 28 dpi. In the nymphs infected by artificial feeding, the transstadial transmission of WNV was confirmed molecularly in 46.7% of males, while virus transmission during in vitro feeding of I. ricinus females originating from infected nymphs was not registered. The long persistence of WNV in I. ricinus ticks did not correlate with the transmission of the virus and it is unlikely that I. ricinus represents a competent vector. However, there is a potential reservoir role that this tick species can play, with hosts potentially acquiring the viral agent after ingesting the infected ticks.

DC-SIGN enhances infection of cells with glycosylated West Nile virus in vitro and virus replication in human dendritic cells induces production of IFN-α and TNF-α

2008 ◽  
Vol 135 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Byron E.E. Martina ◽  
Penelopie Koraka ◽  
Petra van den Doel ◽  
Guus F. Rimmelzwaan ◽  
Bart L. Haagmans ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
West Nile Virus ◽  
Virus Replication ◽  
West Nile ◽  
Tnf Α ◽  
Human Dendritic Cells

scholarly journals Mutations in West Nile virus nonstructural proteins that facilitate replicon persistence in vitro attenuate virus replication in vitro and in vivo

Virology ◽  
2007 ◽  
Vol 364 (1) ◽  
pp. 184-195 ◽  
Author(s):  
Shannan L. Rossi ◽  
Rafik Fayzulin ◽  
Nathan Dewsbury ◽  
Nigel Bourne ◽  
Peter W. Mason
Keyword(s):  
West Nile Virus ◽  
Virus Replication ◽  
Nonstructural Proteins ◽  
West Nile
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