The smallpox virus was already circulating in Northern Europe in the 7th century. This is indicated by DNA from Viking skeletons that researchers from Charité - Universitätsmedizin Berlin, including DZIF scientists, the University of Cambridge and the University of Copenhagen have now analysed. This is the first scientific proof that the smallpox virus has been infecting humans for at least 1,400 years. The unexpected genetic diversity of the virus could also be relevant for the future.
The variola virus, which causes smallpox, is regarded as the deadliest virus worldwide: in the 20th century alone, 300 to 500 million people died of the disease and the mortality rate was up to 30 percent. The human smallpox virus was declared extinct in 1980 after a worldwide vaccination campaign. Nevertheless, there are still cases today in Central and West Africa in which the related monkeypox virus is transmitted to humans - with comparable symptoms but lower mortality than with true smallpox.
It has not yet been clarified how long the human smallpox virus actually circulated before its eradication. Historical writings suggest that smallpox may have existed more than 3,000 years ago. However, the oldest skeleton in which the virus could be genetically identified was only about 360 years old. "So there was a discrepancy of almost 3,000 years between what is generally assumed about the history of the smallpox virus and what is actually known about it," explains bioinformatician Dr. Terry Jones, head of a research group at the Institute of Virology on the Charité Mitte campus and DZIF scientist. Together with colleagues from the Lundbeck Foundation GeoGenetics Centre at the University of Copenhagen and the University of Cambridge, he led the study. "So we tried to use modern molecular biological methods to find scientific evidence for the written evidence of an earlier occurrence of smallpox," says Dr. Jones. The approach was successful: the team discovered the variola virus in bones up to 1,400 years old from Viking burial sites in Denmark, Norway, Sweden, Russia and England.
For their analysis, the scientists examined the genetic material of almost 1,900 skeletons that were between 150 and more than 30,000 years old and found in Europe and America. In 13 cases they succeeded in enriching DNA fragments of the human smallpox virus from the teeth or part of the temporal bone of the deceased. The specific ageing damage to the genetic material proved that the DNA was indeed old. Eleven of the people in whom the virus could be detected had lived between about 600 and 1050 AD - i.e. also during the Viking Age (793 to 1066 AD). "Our study thus provides the first molecular biological proof that the Vikings were already infected by the smallpox virus," says the first author of the publication Dr. Barbara Mühlemann, scientist at the German Center for Infection Research (DZIF) at the Institute of Virology on the Charité Mitte campus. "We were thus able to reduce the discrepancy between historical anecdotes and direct evidence of smallpox by about 1,000 years. But we believe it's very likely that there have been previous infections."
The new research results contradict various previous assumptions according to which smallpox, for example, was first brought to Europe by returning crusaders in the 11th to 13th centuries. "On the basis of the smallpox cases in northern Europe that have now been proven and historical accounts of suspected cases in southern and western Europe, we assume that the smallpox virus has been circulating widely in Europe since the end of the Viking Age at the latest," summarises Dr Mühlemann.
Some of the samples were so well preserved that the researchers were able to reconstruct the complete sequence of the virus genome on the computer using the extracted fragments. The analysis of the sequences showed that the smallpox virus, which was active during the Viking era, was clearly different from the variola virus of the 20th century - and more similar to the smallpox viruses that circulate today in camels and gerbils. The old virus had a completely different pattern of active and inactive genes. "Some of these genes influence, among other things, the specificity of pox viruses for their host," explains Dr. Mühlemann. "The activity pattern in the smallpox virus of the Viking Age could mean that the virus could then infect not only humans but also animals." It is not possible to deduce how high the mortality rate was or what symptoms the old virus caused - even though the genetic data suggest that the virus might also have caused fever in the Vikings.
"We had not expected such genetic diversity in the human smallpox virus, which really surprised us," says Dr. Jones, who is also a DZIF scientist and a Senior Research Associate at the University of Cambridge. "The evolution of the smallpox virus is much more complex than we had assumed. If the human smallpox virus followed such different genetic paths in the past, the animal pox viruses that are still circulating could have developed in a similarly broad range - with possible consequences for the transmission of the disease from animals to humans. We should therefore keep a closer eye on the animal pox viruses in the future. This includes closely monitoring outbreaks of the monkeypox virus and finding out from which animal the virus is transmitted to humans.
About the study
Dr. Jones led the current study together with Prof. Dr. Eske Willerslev (St. John's College, University of Cambridge, The Lundbeck Foundation GeoGenetics Centre, University of Copenhagen) and Prof. Dr. Martin Sikora (The Lundbeck Foundation GeoGenetics Centre, University of Copenhagen). Besides Dr. Mühlemann, Dr. Lasse Vinner (The Lundbeck Foundation GeoGenetics Centre of the University of Copenhagen) was the second first author of the study. Dr. Mühlemann worked on the project both as part of her doctoral thesis at the University of Cambridge and as a postdoctoral fellow in Dr. Jones' team at the Charité. The study is part of a long-term project of the Lundbeck Foundation GeoGenetics Centre for the sequencing of 5,000 old human genomes.
Genuine smallpox is caused by the Variola virus and is transmitted by droplet infection. Typical symptoms include fever and blistering of the skin surface. The mortality rate is up to 30 percent. Many of the survivors are scarred for life. The characteristic skin changes leave scars, and the disease can also lead to hearing loss or blindness.
Source: Charité press release