Prediction of steps in the evolution of variola virus host range

PLoS One. 2014 Mar 13;9(3):e91520. doi: 10.1371/journal.pone.0091520. eCollection 2014.

Abstract

Variola virus, the agent of smallpox, has a severely restricted host range (humans) but a devastatingly high mortality rate. Although smallpox has been eradicated by a World Health Organization vaccination program, knowledge of the evolutionary processes by which human super-pathogens such as variola virus arise is important. By analyzing the evolution of variola and other closely related poxviruses at the level of single nucleotide polymorphisms we detected a hotspot of genome variation within the smallpox ortholog of the vaccinia virus O1L gene, which is known to be necessary for efficient replication of vaccinia virus in human cells. These mutations in the variola virus ortholog and the subsequent loss of the functional gene from camelpox virus and taterapox virus, the two closest relatives of variola virus, strongly suggest that changes within this region of the genome may have played a key role in the switch to humans as a host for the ancestral virus and the subsequent host-range restriction that must have occurred to create the phenotype exhibited by smallpox.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • DNA, Viral / genetics
  • Evolution, Molecular*
  • Genes, Viral
  • Genetic Variation
  • Genome
  • Genome, Viral*
  • Host Specificity / genetics
  • Humans
  • Mutation
  • Phylogeny
  • Polymorphism, Single Nucleotide
  • Poxviridae / genetics
  • Vaccinia virus / genetics
  • Variola virus / genetics*

Substances

  • Amino Acids
  • DNA, Viral

Grants and funding

This study was funded by a Natural Sciences and Engineering Research Council Discovery Grant to CU (#155125; www.nserc-crsng.gc.ca). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.