The rediscovery of smallpox.

Area of Science:

• Virology
• Paleomicrobiology
• Genomics

Background:

• Smallpox, a human-exclusive infectious disease caused by a poxvirus, historically had a high mortality rate (30% for Variola major).
• Early prevention methods included variolation and quarantine, preceding Edward Jenner's vaccination advancements in the 18th century.
• The World Health Organization declared smallpox eradicated in 1980 after extensive global vaccination campaigns.

Observation:

• Microscopy enabled early 20th-century structural characterization of the smallpox virus.
• By 1990, smallpox virus genomes were sequenced, allowing classification and investigation of origins and evolution.
• Current research on smallpox evolution is limited to 20th-century viral genomes.

Findings:

• Recent detection of fragmented poxvirus genomes has enabled the description of a new smallpox virus phylogeny.
• Analysis of these fragmented ancient genomes offers novel insights into the genetic evolution of poxviruses.
• The study of ancient smallpox viral strains presents an exceptional opportunity to explore the disease's natural history.

Implications:

• Understanding the genetic evolution of ancient smallpox strains can inform future research on viral pathogens.
• Paleomicrobiological studies of smallpox could reveal crucial information about its historical diffusion and adaptation.
• Investigating ancient viral genomes is essential for understanding the long-term evolutionary trajectory of diseases like smallpox.