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.

Keywords: ancient DNA; paleo virology; parvovirus B19; virology; virus evolution.

Fig. 1.

Geographic locations of the samples with reads matching B19V. Samples are colored by age. Squares indicate genotype 1, circles genotype 2. Empty symbols indicate samples with 30–50% coverage of the coding region, filled symbols samples with >50% coverage of the coding region that were included for further analysis. Samples that were negative for B19V are shown as small gray symbols (samples outside Eurasia are omitted for clarity).

Fig. 2.

Maximum clade credibility tree inferred in BEAST2. A strict clock and coalescent Bayesian skyline population prior were used. The substitution rate is inferred as 1.22 × 10⁻⁵ s/s/y (95% HPD interval, 1.04 × 10⁻⁵–1.40 × 10⁻⁵ s/s/y), and the root age as 10.1 kya (95% HPD interval, 9.0–11.3 kya). The x axis denotes time into the past, in years. Taxon names: genotype/historical period, accession number/sample identifier, sample age, country abbreviation of sequence origin and region of sequence origin, as determined by the Standard country or area codes for statistical use (42). Horizontal gray bars indicate 95% HPD intervals of node ages.

Fig. 3.

Trees inferred using BEAST2 from different regions of the B19V genome. Trees were inferred using a strict clock and coalescent Bayesian skyline population prior. Positions of ancient genotype 1 and ancient genotype 2 sequences are shown as blue or red tips, respectively. Collapsed modern genotype 1, 2, and 3 sequences are shown as blue, red, and yellow dots, respectively. 95% HPD intervals of node ages are shown by gray horizontal bars. The x axis denotes time into the past, in years. Vertical gray dashed lines indicate, from left to right, the maximum height of the root and the maximum and minimum height of the genotype 3 clade. (A) Tree from Fig. 2 using the full coding region. (B) Tree using the full coding region, excluding genotype 2 sequences. (C) Tree using the minor parent (positions 1,877–3,352 of the alignment). (D) Tree using the major parent (positions 1–1,876 and 3,353–4,354 of the alignment).