Cryo-EM-based discovery of a pathogenic parvovirus causing epidemic mortality by black wasting disease in farmed beetles

Cell. 2024 Oct 3;187(20):5604-5619.e14. doi: 10.1016/j.cell.2024.07.053. Epub 2024 Aug 28.

Abstract

We use cryoelectron microscopy (cryo-EM) as a sequence- and culture-independent diagnostic tool to identify the etiological agent of an agricultural pandemic. For the past 4 years, American insect-rearing facilities have experienced a distinctive larval pathology and colony collapse of farmed Zophobas morio (superworm). By means of cryo-EM, we discovered the causative agent: a densovirus that we named Zophobas morio black wasting virus (ZmBWV). We confirmed the etiology of disease by fulfilling Koch's postulates and characterizing strains from across the United States. ZmBWV is a member of the family Parvoviridae with a 5,542 nt genome, and we describe intersubunit interactions explaining its expanded internal volume relative to human parvoviruses. Cryo-EM structures at resolutions up to 2.1 Å revealed single-strand DNA (ssDNA) ordering at the capsid inner surface pinned by base-binding pockets in the capsid inner surface. Also, we demonstrated the prophylactic potential of non-pathogenic strains to provide cross-protection in vivo.

Keywords: Zophobas morio; capsid structure; capsid-DNA interactions; cryo-EM; densovirus; diagnostic virology; emerging infectious diseases; entomology; parvovirus; superworm.

MeSH terms

  • Animals
  • Capsid / chemistry
  • Capsid / metabolism
  • Capsid / ultrastructure
  • Capsid Proteins / chemistry
  • Capsid Proteins / genetics
  • Capsid Proteins / metabolism
  • Coleoptera* / virology
  • Cryoelectron Microscopy*
  • DNA, Single-Stranded / chemistry
  • Densovirus / chemistry
  • Densovirus / genetics
  • Genome, Viral
  • Larva / virology
  • Models, Molecular
  • Parvoviridae Infections / epidemiology
  • Parvoviridae Infections / veterinary
  • Parvoviridae Infections / virology
  • Parvovirus / chemistry
  • Parvovirus / genetics
  • Phylogeny

Substances

  • DNA, Single-Stranded
  • Capsid Proteins