Role of the mutant spectrum in adaptation and replication of West Nile virus

Abstract

West Nile virus (WNV) has successfully spread throughout the USA, Canada, Mexico, the Caribbean and parts of Central and South America since its 1999 introduction into North America. Despite infecting a broad range of both mosquito and avian species, the virus remains highly genetically conserved. This lack of evolutionary change over space and time is common with many arboviruses and is frequently attributed to the adaptive constraints resulting from the virus cycling between vertebrate hosts and invertebrate vectors. WNV, like most RNA viruses studied thus far, has been shown in nature to exist as a highly genetically diverse population of genotypes. Few studies have directly evaluated the role of these mutant spectra in viral fitness and adaptation. Using clonal analysis and reverse genetics experiments, this study evaluated genotype diversity and the importance of consensus change in producing the adaptive phenotype of WNV following sequential mosquito cell passage. The results indicated that increases in the replicative ability of WNV in mosquito cells correlate with increases in the size of the mutant spectrum, and that consensus change is not solely responsible for alterations in viral fitness and adaptation of WNV. These data provide evidence of the importance of quasispecies dynamics in the adaptation of a flavivirus to new and changing environments and hosts, with little evidence of significant genetic change.

Host Alternation of Chikungunya Virus Increases Fitness while Restricting Population Diversity and Adaptability to Novel Selective Pressures

“…Coincident increases in intrahost West Nile virus (WNV) diversity and fitness after serial or alternating vertebrate and invertebrate passage show that minority genomes can augment fitness (5,(20)(21)(22). Consistent with these studies, we found that CHIKV genetic diversity significantly increased after both serial and alternating passage (Fig.…”

“…This suggests that fitness increases were mediated by minority genomes in the mutant spectrum. However, a major limitation of the in vivo experiments and other arbovirus evolution studies is that sequencing of individual RNAs from the mutant spectrum in passaged intrahost populations was not performed (although notable exceptions for flaviviruses exist [5,22]). The identity of minority variants within intrahost arbovirus populations and their influences on phenotype have not been extensively examined.…”

Free-living pathogens: Life-history constraints and strain competition

“…Ecologically, inclusion of a freeliving stage in the pathogen life cycle can separate time scales of within-host reproduction and between-host transmission, complicating the host-pathogen dynamics. Vector-borne pathogens may have to adapt to differing biologies of their host and living vector, and the difference presumably demands evolutionary compromise (Ciota et al, 2007). Pathogens with a free-living stage face parallel challenges, since adaptations advancing the rate of host exploitation might impair the free-living form's persistence.…”

Hidden Virulence Determinants in a Viral Quasispecies In Vivo

“…This has been clearly evidenced by variations in viral diversity brought about by the copying fidelity of the viral polymerase, which may modulate viral virulence in vivo (39,57). A role of the mutant spectrum in viral pathogenesis has been also evidenced for West Nile virus infections (9,29). Knowledge of the evolutionary dynamics of viral populations in vivo is key to understanding viral pathogenesis.…”