Dynamic evolution in the key honey bee pathogen deformed wing virus: Novel insights into virulence and competition using reverse genetics

PLoS Biol. 2019 Oct 10;17(10):e3000502. doi: 10.1371/journal.pbio.3000502. eCollection 2019 Oct.

Abstract

The impacts of invertebrate RNA virus population dynamics on virulence and infection outcomes are poorly understood. Deformed wing virus (DWV), the main viral pathogen of honey bees, negatively impacts bee health, which can lead to colony death. Despite previous reports on the reduction of DWV diversity following the arrival of the parasitic mite Varroa destructor, the key DWV vector, we found high genetic diversity of DWV in infested United States honey bee colonies. Phylogenetic analysis showed that divergent US DWV genotypes are of monophyletic origin and were likely generated as a result of diversification after a genetic bottleneck. To investigate the population dynamics of this divergent DWV, we designed a series of novel infectious cDNA clones corresponding to coexisting DWV genotypes, thereby devising a reverse-genetics system for an invertebrate RNA virus quasispecies. Equal replication rates were observed for all clone-derived DWV variants in single infections. Surprisingly, individual clones replicated to the same high levels as their mixtures and even the parental highly diverse natural DWV population, suggesting that complementation between genotypes was not required to replicate to high levels. Mixed clone-derived infections showed a lack of strong competitive exclusion, suggesting that the DWV genotypes were adapted to coexist. Mutational and recombination events were observed across clone progeny, providing new insights into the forces that drive and constrain virus diversification. Accordingly, our results suggest that Varroa influences DWV dynamics by causing an initial selective sweep, which is followed by virus diversification fueled by negative frequency-dependent selection for new genotypes. We suggest that this selection might reflect the ability of rare lineages to evade host defenses, specifically antiviral RNA interference (RNAi). In support of this hypothesis, we show that RNAi induced against one DWV strain is less effective against an alternate strain from the same population.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Arachnid Vectors / virology*
  • Bees / genetics
  • Bees / immunology
  • Bees / parasitology
  • Bees / virology*
  • Clone Cells
  • Gene Library
  • Genetic Variation
  • Genotype
  • Immune Evasion / genetics*
  • Mutation
  • Phylogeny
  • RNA Interference / immunology
  • RNA Viruses / classification
  • RNA Viruses / genetics*
  • RNA Viruses / immunology
  • RNA Viruses / pathogenicity
  • Recombination, Genetic
  • Reverse Genetics / methods
  • Selection, Genetic
  • Varroidae / virology*
  • Virulence
  • Virus Replication

Supplementary concepts

  • Deformed wing virus

Grants and funding

This research was supported by the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) grant 2017-06481 (EVR, YPC and JDE) and the USDA Animal and Plant Health Inspection Service (APHIS) agreements 19-8130-0745-IA and 18-8130-0787-IA. Genomic analyses used resources provided by the USDA-Agricultural Research Service (ARS) SCINet project, ARS project number 0500-00093-001-00-D. USDA is an equal opportunity provider and employer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.