The skin marks observed on the mummy of Ramses V, who died in 1757 BC, suggest that ancient Egypt may have been a region where the smallpox virus (Variola major virus or VARV) was already circulating . But despite these observations and written records, this age is not yet proven.
Until now, the oldest genetic reference to this virus dates back to the 17th century, a period to which a Lithuanian mummy belongs, from which a genomic sequence of the virus was isolated. However, both the origin and evolution of the virus, which alone caused between 300 and 500 million deaths worldwide, remain a mystery.
New research, now published in the journal Science, provides evidence about 1,000 years older than it was, thanks to the sequencing of the virus genome in 11 individuals who lived during the Viking age (between the years 600 and 1000) to the north Europe. The work has also allowed the almost complete reconstruction of the virus genome in four of them from human teeth and bones.
“Smallpox was already widely circulating in 600 in that region and, therefore, in the rest of the continent. This refutes claims that the virus was only introduced and endemic after medieval times, ”says Martin Sikora , professor at the Globe Institute at the University of Copenhagen in Denmark and lead author of the study.
In the 20th century, the disease – with a mortality of more than 30% – became one of the most virulent and devastating in history, but it was the first and only one to be eliminated in the entire human population, as certified by the Organization. World Health Organization ( wHO ) in 1980. However, those last pandemic strains that circulated during the last century genetically different from those that have now been found in the Vikings.
“The virus that circulated during the Viking era was genetically quite different from the last pandemic strains of the 20th century. These were divided about 1,700 years ago and then died out sometime after the Viking era, “continues Sikora.
According to Antonio Alcamí , a researcher at the CSIC Severo Ochoa Molecular Biology Center and the Autonomous University of Madrid, who publishes an article in perspective on this research in the journal, the strain that has been sequenced disappeared and did not arrive to this day. “The one that arrived was another,” he told SINC.
Reconstructing the evolution of the virus
The VARV lineages found in the Vikings represent a diverse, now extinct, brother clade of the modern smallpox virus. It may have spread to northern Europe for centuries before becoming the highly virulent and deadly strain of the past century. “The virus that causes smallpox existed in a very different way, at least genetically, for a period of more than 400 years,” says Terry Jones , a researcher at the Center for Pathogen Evolution in the University’s Department of Zoology. from Cambridge.
Scientists assume that the virus arose in an animal, specifically a rodent, and that it possibly passed through an intermediate animal, such as a cow, to humans. “It is not known where this happened or when. The virus may have been transmitted to humans many times, without sustained transmission between them. That is what is happening now with monkeypox, as seen in a dozen countries in central and western Africa, “says Jones.
The study makes it possible to track the genetic changes that have occurred during the evolution of the virus, from a common ancestor with the closest animal strains and after the division of the strains in the Viking era. “This information tells us how the virus has adapted to humans at the molecular level during its history, and therefore also why it could have become so virulent,” Sikora said.
Variola major virus was not only very virulent, but also lost 29 genes compared to an ancient virus. Between 600 and 1000, however, the virus had only lost half. With this finding, a “unique phenomenon” is observed in virology. “The virus has not only maintained its virulence, but has lost a lot of genes. In the case of the viruses sequenced now, they have lost half of the genes, and this suggests that at that time the virus was halfway between something that had all the genes and the virus of the 20th century ”, explains Alcamí.
Lessons learned for SARS-CoV-2
This study reveals certain similarities with SARS-CoV-2 , the virus responsible for the current pandemic. Epidemics of diseases caused by animal zoonoses have affected human populations much earlier than previously thought. “The current coronavirus outbreak is just another example of this,” Sikora told SINC. Virologists have been saying for many years “that we should be alert to the possibility of zoonoses and that more should be invested in surveillance,” warns the researcher.
“We know that there are a variety of potentially dangerous viruses in animals that humans often come into contact with (smallpox rodents, coronavirus bats; or intermediate animals). Current findings delve into the importance of surveillance and search for reservoir species, ”says Jones.
The researcher again gives an example of monkey pox: “It is clearly dangerous, it can jump on humans, but we still don’t know what species it comes from!” Their findings now published in Science emphasize what virologists have been saying for many years; “That we must be attentive to the possibility of zoonosis and that more should be invested in surveillance”, alerts the researcher.
On the other hand, according to Alcamí, when a virus jumps from an animal to the human being, it is very common that it is very virulent from the first moment, as has been observed in other diseases such as Ebola or COVID-19 . “This occurs because the pathogen has not become accustomed to the human immune system and does not know how to manage the situation,” he says.
However, for the expert “it is transmission that dictates the future of a virus, rather than virulence or attenuation.” In short, based on the known case of the smallpox virus – which has not lost its virulence over the years -, the expert assures that “it is not certain that a virus like SARS-CoV-2 will be attenuated. It is necessary to be vigilant ”, he concludes.