Monday, July 27, 2020

Viking Era Smallpox DNA

Somebody decided that "the Viking Age" sounded like a better time descriptor to put in the title of their paper than that time period's other common name, "the Dark Ages." 

Reading between the lines, one of the big questions being asked is whether smallpox suddenly evolved to become more deadly and virulent sometime in the 1600s.
Scientists have discovered extinct strains of smallpox in the teeth of Viking skeletons -- proving for the first time that the killer disease plagued humanity for at least 1400 years.
Smallpox spread from person to person via infectious droplets, killed around a third of sufferers and left another third permanently scarred or blind. Around 300 million people died from it in the 20th century alone before it was officially eradicated in 1980 through a global vaccination effort -- the first human disease to be wiped out.
Now an international team of scientists have sequenced the genomes of newly discovered strains of the virus after it was extracted from the teeth of Viking skeletons from sites across northern Europe. . . .
Smallpox was eradicated throughout most of Europe and the United States by the beginning of the 20th century but remained endemic throughout Africa, Asia, and South America. The World Health Organisation launched an eradication programme in 1967 that included contact tracing and mass communication campaigns -- all public health techniques that countries have been using to control today's coronavirus pandemic. But it was the global roll out of a vaccine that ultimately enabled scientists to stop smallpox in its tracks.
Historians believe smallpox may have existed since 10,000 BC but until now there was no scientific proof that the virus was present before the 17th century. It is not known how it first infected humans but, like Covid-19, it is believed to have come from animals. . . . 
The team of researchers found smallpox -- caused by the variola virus -- in 11 Viking-era burial sites in Denmark, Norway, Russia, and the UK. They also found it in multiple human remains from Öland, an island off the east coast of Sweden with a long history of trade. The team were able to reconstruct near-complete variola virus genomes for four of the samples. . . .
"The early version of smallpox was genetically closer in the pox family tree to animal poxviruses such as camelpox and taterapox, from gerbils. It does not exactly resemble modern smallpox which show that virus evolved. We don't know how the disease manifested itself in the Viking Age -- it may have been different from those of the virulent modern strain which killed and disfigured hundreds of millions."
Dr Terry Jones, one of the senior authors leading the study, a computational biologist based at the Institute of Virology at Charité -- Universitätsmedizin Berlin and the Centre for Pathogen Evolution at the University of Cambridge, said: "There are many mysteries around poxviruses. To find smallpox so genetically different in Vikings is truly remarkable. No one expected that these smallpox strains existed. It has long been believed that smallpox was in Western and Southern Europe regularly by 600 AD, around the beginning of our samples.
"We have proved that smallpox was also widespread in Northern Europe. Returning crusaders or other later events have been thought to have first brought smallpox to Europe, but such theories cannot be correct. While written accounts of disease are often ambiguous, our findings push the date of the confirmed existence of smallpox back by a thousand years."
From Science Daily.
Viking smallpox diversity 
Humans have a notable capacity to withstand the ravages of infectious diseases. Smallpox killed millions of people but drove Jenner's invention of vaccination, which eventually led to the annihilation of this virus, declared in 1980. 
To investigate the history of smallpox, Mühlemann et al. obtained high-throughput shotgun sequencing data from 1867 human remains ranging from >31,000 to 150 years ago (see the Perspective by Alcamí). Thirteen positive samples emerged, 11 of which were northern European Viking Age people (6th to 7th century CE). Although the sequences were patchy and incomplete, four could be used to infer a phylogenetic tree. This showed distinct Viking Age lineages with multiple gene inactivations. The analysis pushes back the date of the earliest variola infection in humans by ∼1000 years and reveals the existence of a previously unknown virus clade.
Science, this issue p. eaaw8977; see also p. 376 
Structured Abstract 
INTRODUCTION 
Variola virus (VARV), the causative agent of smallpox, is estimated to have killed between 300 million and 500 million people in the 20​th century and was responsible for widespread mortality and suffering for at least several preceding centuries. Humans are the only known host of VARV, and smallpox was declared eradicated in 1980. The timeline of the emergence of smallpox in humans is unclear. Based on sequence data up to 360 years old, the most recent common ancestor of VARV has been dated to the 16th or 17th century. This contrasts with written records of possible smallpox infections dating back at least 3000 years and mummified remains suggestive of smallpox dating to 3570 years ago. 
RATIONALE 
Ancient virus sequences recovered from archaeological remains provide direct molecular evidence of past infections, give detail of genetic changes that have occurred during the evolution of the virus, and can reveal viable virus sequence diversity not currently present in modern viruses. In the case of VARV, ancient sequences may also reduce the gap between the written historical record of possible early smallpox infections and the dating of the oldest available VARV sequences. We therefore screened high-throughput shotgun sequencing data from skeletal and dental remains of 1867 humans living in Eurasia and the Americas between ~31,630 and ~150 years ago for the presence of sequences matching VARV. 
RESULTS 
VARV sequences were recovered from 13 northern European individuals, including 11 dated to ~600–1050 CE, overlapping the Viking Age, and we reconstructed near-complete VARV genomes for four of them. The samples predate the earliest confirmed smallpox cases by ~1000 years. Eleven of the recovered sequences fall into a now-extinct sister clade of the modern VARVs in circulation prior to the eradication of smallpox, while two sequences from the 19th century group with modern VARV. The inferred date of the most recent common ancestor of VARV is ~1700 years ago.
The number of functional genes is generally reduced in orthopoxviruses with narrow host ranges. A comparison of the gene content of the Viking Age sequences shows great contrast with that of modern VARV. 
Three genes that are active in all modern VARV sequences were inactive over 1000 years ago in some or all ancient VARV. Among 10 genes inactive in modern and Viking Age VARV, the mutations causing the inactivations are different and the genes are predicted to be active in the ancestor of both clades, suggesting parallel evolution. Fourteen genes inactivated in modern VARV are active in some or all of the ancient sequences, eight of which encode known virulence factors or immunomodulators. 
The active gene counts of the four higher-coverage Viking Age viral genomes provide snapshots from an ~350-year period, showing the reduction of gene content during the evolution of VARV. These genomes support suggestions that orthopoxvirus species derive from a common ancestor containing all genes present in orthopoxviruses today, with the reduction in active gene count conjectured to be the result of long-term adaptation within host species.
CONCLUSION 
The Viking Age sequences reported here push the definitive date of the earliest VARV infection in humans back by ~1000 years. These sequences, combined with early written records of VARV epidemics in southern and western Europe, suggest a pan-European presence of smallpox from the late 6th century. The ancient viruses are part of a previously unknown, now-extinct virus clade and were following a genotypic evolutionary path that differs from modern VARV. The reduction in gene content shows that multiple combinations of active genes have led to variola viruses capable of circulating widely within the human population.
Barbara Mühlemann, et al., "Diverse variola virus (smallpox) strains were widespread in northern Europe in the Viking Age." 369 (6502) Science eaaw8977 (July 24, 2020).

The companion commentary and its abstract are as follows:
Smallpox—caused by variola virus (VARV), a poxvirus—was one of the most virulent diseases known to humans, killing up to 30% of infected individuals and 300 million to 500 million people in the 20th century. The year 2020 commemorates the 40th anniversary of smallpox eradication, the first human disease eradicated after a global vaccination campaign led by the World Health Organization (WHO). The last samples of VARV are kept in two high-security laboratories pending destruction, and fears about reemergence or deliberate release of VARV have not subsided (1). Smallpox eradication is one of the most successful stories of public health, but the origin of the deadly virus remains an enigma. On page 391 of this issue, Mühlemann et al. (2) report the identification of VARV in archaeological remains from the Viking Age (600 to 1050 CE) that reveals new information about the origin of VARV and its evolution in human populations.

Antonio Alcamí, "Was smallpox a widespread mild disease?" 369 (6503) Science 376-377 (June 24, 2020).

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