Evolutionary and phenotypic analysis of live virus isolates suggests arthropod origin of a pathogenic RNA virus family

Proc Natl Acad Sci U S A. 2015 Jun 16;112(24):7536-41. doi: 10.1073/pnas.1502036112. Epub 2015 Jun 2.

Abstract

The evolutionary origins of arboviruses are unknown because their typical dual host tropism is paraphyletic within viral families. Here we studied one of the most diversified and medically relevant RNA virus families, the Bunyaviridae, in which four of five established genera are transmitted by arthropods. We define two cardinally novel bunyavirus groups based on live isolation of 26 viral strains from mosquitoes (Jonchet virus [JONV], eight strains; Ferak virus [FERV], 18 strains). Both viruses were incapable of replicating at vertebrate-typical temperatures but replicated efficiently in insect cells. Replication involved formation of virion-sense RNA (vRNA) and mRNA, including cap-snatching activity. SDS/PAGE, mass spectrometry, and Edman degradation identified translation products corresponding to virion-associated RNA-dependent RNA polymerase protein (RdRp), glycoprotein precursor protein, glycoproteins Gn and Gc, as well as putative nonstructural proteins NSs and NSm. Distinct virion morphologies suggested ancient evolutionary divergence, with bunyavirus-typical morphology for FERV (spheres of 60-120 nm) as opposed to an unusual bimorphology for JONV (tubular virions of 60 × 600 nm and spheres of 80 nm). Both viruses were genetically equidistant from all other bunyaviruses, showing <15% amino acid identity in the RdRp palm domain. Both had different and unique conserved genome termini, as in separate bunyavirus genera. JONV and FERV define two novel sister taxons to the superclade of orthobunyaviruses, tospoviruses, and hantaviruses. Phylogenetic ancestral state reconstruction with probabilistic hypothesis testing suggested ancestral associations with arthropods at deep nodes throughout the bunyavirus tree. Our findings suggest an arthropod origin of bunyaviruses.

Keywords: ancestral reconstruction; arbovirus; bunyavirus; insect-specific virus; virus evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arboviruses / classification*
  • Arboviruses / genetics*
  • Arboviruses / pathogenicity
  • Base Sequence
  • Bunyaviridae / classification*
  • Bunyaviridae / genetics*
  • Bunyaviridae / pathogenicity
  • Cell Line
  • Conserved Sequence
  • Culicidae / virology*
  • Endonucleases / genetics
  • Evolution, Molecular
  • Genome, Viral
  • Host Specificity
  • Microscopy, Electron
  • Molecular Sequence Data
  • Phenotype
  • Phylogeny
  • RNA, Viral / genetics
  • RNA-Dependent RNA Polymerase / genetics
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Temperature
  • Viral Proteins / genetics

Substances

  • RNA, Viral
  • Viral Proteins
  • RNA-Dependent RNA Polymerase
  • Endonucleases

Associated data

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