Abstract
Our current understanding of the natural evolution of RNA viruses comes largely from consensus level genetic analyses which ignore the diverse mutant swarms that comprise within-host viral populations. The breadth and composition of viral mutant swarms impact viral fitness and adaptation, and the capacity for swarm plasticity is likely to be particularly important for arthropod-borne viruses (arboviruses) that cycle between taxonomically divergent hosts. Despite this, characterization of the relationship between the selective pressures and genetic signatures of the mutant swarm and consensus sequences is lacking. To clarify this, we analyzed previously generated whole genome, deep-sequencing data from 548 West Nile virus samples isolated from avian tissues or mosquitoes in New York State from 1999–2018. Both consensus level (interhost) and minority level (intrahost) nucleotide and amino acid sequences were analyzed, and diversity at each position was calculated across the genome in order to assess the relationship between minority and consensus sequences for individual genes and hosts. Our results indicate that consensus sequences are an inept representation of the overall genetic diversity. Unique host and gene-specific signatures and selective pressures were identified. These data demonstrate that an accurate and comprehensive understanding of arbovirus evolution and adaptation within and between hosts requires consideration of minority genotypes.
Highlights
The genus Flavivirus consists of arthropod-borne viruses of significant public health importance, collectively causing over fifty million cases annually worldwide [1]
To address how inter and intrahost diversity are related in West Nile virus (WNV), we analyzed 548 whole-genome sequences with sufficient depth, out of a total of 588 possible isolates (Supplementary Table S1)
Genome-wide analysis of 270 mosquito isolates and 276 avian isolates of WNV identified a total of 25,503 unique single nucleotide polymorphisms (SNPs) and 4702 unique amino acids (AA) substitutions on the interhost level, and a total of 380,537 unique SNPs and 151,265 unique AA substitutions on the intrahost level
Summary
The genus Flavivirus consists of arthropod-borne viruses (arboviruses) of significant public health importance, collectively causing over fifty million cases annually worldwide [1]. West Nile virus (WNV) is a mosquito-borne positive-sense single-stranded RNA virus of the family Flaviviridae and the genus Flavivirus [2]. It is considered an emerging infectious disease and is the most geographically widespread of the flaviviruses which include Zika (ZIKV), yellow fever (YFV) and dengue (DENV). Due to its rapid geographic spread and resultant public health burden in newly affected countries, WNV is considered to be among the most widespread and prevalent causative agent of viral encephalitis worldwide [4].
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