Ancient human parvovirus B19 in Eurasia reveals its long-term association with humans

Abstract

Human parvovirus B19 (B19V) is a ubiquitous human pathogen associated with a number of conditions, such as fifth disease in children and arthritis and arthralgias in adults. B19V is thought to evolve exceptionally rapidly among DNA viruses, with substitution rates previously estimated to be closer to those typical of RNA viruses. On the basis of genetic sequences up to ∼70 years of age, the most recent common ancestor of all B19V has been dated to the early 1800s, and it has been suggested that genotype 1, the most common B19V genotype, only started circulating in the 1960s. Here we present 10 genomes (63.9-99.7% genome coverage) of B19V from dental and skeletal remains of individuals who lived in Eurasia and Greenland from ∼0.5 to ∼6.9 thousand years ago (kya). In a phylogenetic analysis, five of the ancient B19V sequences fall within or basal to the modern genotype 1, and five fall basal to genotype 2, showing a long-term association of B19V with humans. The most recent common ancestor of all B19V is placed ∼12.6 kya, and we find a substitution rate that is an order of magnitude lower than inferred previously. Further, we are able to date the recombination event between genotypes 1 and 3 that formed genotype 2 to ∼5.0-6.8 kya. This study emphasizes the importance of ancient viral sequences for our understanding of virus evolution and phylogenetics.

Ancient pathogen genomics as an emerging tool for infectious disease research

“…Pathogen aDNA is thought to be preserved within the remnants of the pulp chamber, likely as part of desiccated blood 8,17 . Consequently, tooth sampling has proved successful in the retrieval of whole genomes or genome wide data (that is, low coverage genomes that have provided limited analytical resolution) from ancient bacteria such as Y. pestis 20,[30][31][32][33][34][35][36][37][38][39] , Borrelia recurrentis 40 and Salmonella enterica 41 ; ancient eukaryotic pathogens such as Plasmodium falciparum 42 ; and ancient viruses such as hepatitis B virus (HBV) 43,44 and human parvovirus B19 (B19V) 45 . Even M. leprae, which commonly manifests in the chronic form, has been retrieved from ancient teeth 27,28 .…”

“…This technique has contributed to the increased number of specimens from which human genome wide single nucleotide polymorphism (SNP) data could be retrieved 84,85 , even from climate zones that pose challenges to aDNA preservation (pre sented elsewhere [86][87][88] ). In addition, in solutionbased capture has recently become the preferred method for microbial pathogen genome recovery for both bacteria and DNA viruses (for examples, see reFs 34,37,41,43,45,49,50 ). Nevertheless, deep shotgun sequencing alone has also been used for human [89][90][91] and pathogen 28,33,48 high quality…”

“…It is becoming increasingly apparent that, aside from plague, other infectious diseases, such as those caused by HBV 43,44 and B19V 45 (TAble 1), were circulating dur ing the same time periods. Further pathogen screening coupled with a temporal assessment of human immune associated genomic variants 84 may reveal key aspects of disease prevalence and susceptibility during this pivotal period of human history.…”

Long-term virus evolution in nature

“…[As an anecdote, in my experience as a member of the Research Group of the Standing Technical Committee for the Control of FMD of Food and Agriculture Organization of the United Nations (FAO) in the 1980s, FMD outbreaks in any country always came from somewhere else]. A time-dependent bias in evolutionary rates for viruses has been amply documented (Duchene et al, 2014;Aiewsakun and Katzourakis, 2016), including when rates are compared between present-day isolates and those that circulated thousands of years ago (Muhlemann et al, 2018).…”

“…Unfortunately, viruses have not left a fossil record (at least one that we can uncover with the available tools), since according to current paleontology, nitrogen-and phosphorus-rich molecules are unlikely to be protected in fossils older than 1 million years. At most, hundred to thousand years-old skeletal remains or frozen bodies that contain viruses have been analyzed, and sequences retrieved [(Muhlemann et al, 2018) and references therein]. Fortunately, there is a different historical record of ancient viral sequences in the DNA of differentiated organisms, in the form of integrated virus-like genetic elements.…”