17th Century Variola Virus Reveals the Recent History of Smallpox.

Published

Journal Article

Smallpox holds a unique position in the history of medicine. It was the first disease for which a vaccine was developed and remains the only human disease eradicated by vaccination. Although there have been claims of smallpox in Egypt, India, and China dating back millennia [1-4], the timescale of emergence of the causative agent, variola virus (VARV), and how it evolved in the context of increasingly widespread immunization, have proven controversial [4-9]. In particular, some molecular-clock-based studies have suggested that key events in VARV evolution only occurred during the last two centuries [4-6] and hence in apparent conflict with anecdotal historical reports, although it is difficult to distinguish smallpox from other pustular rashes by description alone. To address these issues, we captured, sequenced, and reconstructed a draft genome of an ancient strain of VARV, sampled from a Lithuanian child mummy dating between 1643 and 1665 and close to the time of several documented European epidemics [1, 2, 10]. When compared to vaccinia virus, this archival strain contained the same pattern of gene degradation as 20th century VARVs, indicating that such loss of gene function had occurred before ca. 1650. Strikingly, the mummy sequence fell basal to all currently sequenced strains of VARV on phylogenetic trees. Molecular-clock analyses revealed a strong clock-like structure and that the timescale of smallpox evolution is more recent than often supposed, with the diversification of major viral lineages only occurring within the 18th and 19th centuries, concomitant with the development of modern vaccination.

Full Text

Duke Authors

Cited Authors

  • Duggan, AT; Perdomo, MF; Piombino-Mascali, D; Marciniak, S; Poinar, D; Emery, MV; Buchmann, JP; Duchêne, S; Jankauskas, R; Humphreys, M; Golding, GB; Southon, J; Devault, A; Rouillard, J-M; Sahl, JW; Dutour, O; Hedman, K; Sajantila, A; Smith, GL; Holmes, EC; Poinar, HN

Published Date

  • December 8, 2016

Published In

Volume / Issue

  • 26 / 24

Start / End Page

  • 3407 - 3412

PubMed ID

  • 27939314

Pubmed Central ID

  • 27939314

Electronic International Standard Serial Number (EISSN)

  • 1879-0445

International Standard Serial Number (ISSN)

  • 0960-9822

Digital Object Identifier (DOI)

  • 10.1016/j.cub.2016.10.061

Language

  • eng