Evidence of Smallpox Infection in First Millennium Scandinavian Viking Settlements |

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One of the signal public health achievements/victories of the 20th Century is the eradication of smallpox (variola virus, VARV) announced by the World Health Organization (WHO) in 1980; it has been estimated that smallpox infection killed 300-500 million people in the 20th Century alone.  (A compelling example of the effects of smallpox in 18th Century America can be found in Pox Americana: The Great Smallpox Epidemic of 1775-1782, by Elizabeth A Fenn.)  Fortuitously arriving before the advent of antivaxxers, the Internet, and proliferation of misinformed (at best) amateurs on social media, WHO, supported by most of the Western world was able to track down and subdue (by vaccination) outbreaks of the disease which has no known animal host reservoir.  While a theoretical possibility ever since Jenner used the insight that milkmaids were “naturally” immune due to encountering vaccinia virus from cows in 1796, it took the organization (and relative wealth) of the post-war world and the auspices of the United Nations to remove a viral scourge known from time immemorial.

But how much time is “immemorial”?  There is some evidence (but not definitive) from examination of mummies in Egypt that the disease had arisen 3000-4000 years ago.  Smallpox manifests (besides by causing death) in skin lesions, and very little skin remains after death.  Recently, an international team* of researchers, using genetic technology tools, were able to find smallpox associated with teeth and skeletons from deceased Scandinavians dating to the 6th or 7th Century A.D.  These researchers’ report, entitled “Diverse variola virus (smallpox) strains were widespread in northern Europe in the Viking Age” was published in the scientific journal Science on July 24th.

Variola virus is one of a number of pox viruses in different species (including camels, gerbils, monkeys, mice, and most famously cows), having a linear DNA double stranded genome comprising ~186,000 – ~228,000 basepairs.  The central ~100,000 basepairs encode conserved genes involved in replication and transcription of viral genes, with the terminal portions encoding more host species-specific genes believed to be involved in host range and modulating host immune responses.  The discovery disclosed in this paper was the result of high-throughput shotgun sequencing from 1867 samples from human remains dated from more than 31,000 to 150 years ago.  Twenty-six positive samples were identified but only 13 were amenable to further study (illustrating the difficulty of performing successfully this type of archeological/viral detective work), and 11 of those were from northern Europeans, specifically Viking people from Scandinavia.  These researchers were able to reconstruct almost complete viral genomes from 4 of these samples.  Comparison of the genes present in these samples showed significant (“great contrast”) differences with modern varieties, including 3 genes active in all modern smallpox variants that were inactive in the archeological sample-derived variants.  There are 10 genes inactive in both modern and Viking-Age samples that show different inactivating mutations, and 14 genes inactive in modern variola viruses that were active in the archeological viral samples.  A common theme is the reduction of active genes during the “evolution” of variola virus over time, perhaps due to adaptation to the host species (i.e., us).

The relationship of these genetic inactivations and various subsets of variola variants is shown in this Figure:

2020-07-29 Image
where:

Each row to the right indicates gene status (present, inactivated) in the virus at that level in the cladogram (bottom eight rows), or in an inferred internal node or the root (top seven rows).  The 40 columns represent genes that are either absent or that have an inactivating mutation in at least one of the mVARV (modern) or aVARV (“ancient”) sequences, excluding 19 genes that are absent in both mVARV and aVARV.  Genes are sorted left-to-right by category and then by position in the genome.  Empty circles indicate genes assumed to be present and functional.  Colored circles indicate genes with a gene-inactivating mutation, genes that are absent, or genes that do not have coverage in the ancient sequences (also indicated by an X).  Within a column, genes with identical gene-inactivating mutations are shown in the same color.  Color correspondence between columns carries no meaning.  Genes with partial coverage (in the aVARV sequences) are marked with a black dot.  A horizontal bar across a filled circle indicates a gene-inactivating mutation considered uncertain, because of less than three reads covering the position of the mutation.  A horizontal bar across an empty circle indicates a gene that may be functional (with a length intermediate between its length in viruses where it is functional and viruses where it is not).

Based on these data the researchers determined that these samples belonged to a viral clade previously undetected in modern variola variants and now believed to be extinct.  The researchers posit that this clade was specific for their Viking Age human population and arose from a common ancestor to all variola virus variants.

The authors are cautious in recognizing that these results were obtained from about 2% of the samples studied (525) from this time period, and that Scandinavia in the ~450 years spanning when these samples arose increased in population from ~750,000 to ~ 1 million.  In addition, the very small number of positive samples suggests that there is a large “false negative” rate, due to “differences in DNA preservation, source tissue, or sequencing depth in the screening.”  Accordingly, they note that “it would not be prudent to use the 2% detection rate to estimate smallpox prevalence or fatality rates during the Viking Age.  The likely inaccurate (low) detection rate and the very small sample size argue against regarding prevalence.  Even if all other sources of uncertainty were resolved, it would still not be clear how the figure relates to case fatality rates during that period, because we cannot be sure that the individuals died as a result of their infections.”

Nevertheless, these researchers also recognize the significance of their results in “pushing back” the earliest date of confirmed smallpox incidence from the 17th-18th century to the 6th-7th Century in Europe.  Their results are inconsistent with introduction from other parts of the globe as a result of “returning Crusaders” or “the Moorish invasion of [Spain in] 710 A.D.” “or the invasion of England by the Normans in 1066).  The paper concludes with these thoughts:

The Viking Age sequences reported here push the definitive date of the earliest VARV infection in humans back by ~1000 years and reveal the existence of a previously unknown, now-extinct virus clade.  The ancient viruses were following a genotypic evolutionary path that differs from modern VARV.  This is highlighted by at least three genes inactivated in some aVARV sequences but still active in the mVARV clade, and by 10 genes inactivated in both clades but with gene-inactivating mutations that differ between clades.  The ancient viral genomes show reduction of gene content during the evolution of VARV and that multiple combinations of gene inactivations have led to viruses capable of circulating widely within the human population.

* From the Center for Pathogen Evolution, Department of Zoology, and Department of Pathology, University of Cambridge; Institute of Virology, Charite-Universitatsmedizin, Berlin; German Center for Infection Research, Berlin; Lundbeck Foundation GeoGenetics Center, Section for Evolutionary Genomics and Laboratory of Biological Anthropology, University of Copenhagen; Institute for Molecular Biology, National Academy of Sciences of Armenia; Department of Archeology and Ancient History, Lund University; Sydsvensk Arkeologi, Kristianstad; Department of Human Genetics, University of Chicago; Trace and Environmental DNA Laboratory, Curtin University; Department of Archeology and Cultural History, Norwegian University of Science and Technology; Museum of Cultural History, University of Oslo; Research Institute and Museum of Anthropology and Department of Archeology, Moscow State University; Thames Valley Archeological Services, Reading; Peter the Great Museum of Anthropology and Ethnography, St. Petersburg; Roskilde Museum, Jaegerpris; Malmo Museum, Malmo; Institute for Infectious Diseases and Zoonoses, University of Munich; German Center for Infection Research, Munich; Department of Viroscience, Erasmus Medical Center, Rotterdam; Wellcome Trust Sanger Institute, Hixton; and Danish Institute for Advanced Study, University of Southern Denmark.



www.jdsupra.com2020-07-31 22:05:42

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