Genomic analysis of vaccinia virus strain TianTan provides new insights into the evolution and evolutionary relationships between Orthopoxviruses

•China used a strain of vaccinia virus called TianTan to vaccinate against smallpox.•We describe the complete and corrected DNA sequence of two TianTan virus clones.•The clones bear different symmetrical deletions in the terminal inverted repeats.•In one clone, the deletions oddly inactivate both epidermal growth factor homologs.•TianTan belongs to a phylogenetic clade that includes European vaccinia strains.

Vaccinia virus (VACV) strain TianTan was used for much of China's modern history to vaccinate against smallpox, however the only genome sequence contains errors. We have sequenced additional examples of TianTan to obtain a better picture of this important virus. We detected two different subclones. One (TP03) encodes large deletions in the terminal repeats that extend into both VEGF genes and create a small plaque variant. The second clone (TP05) encodes a nearly intact complement of genes in the terminal repeats, except for an insertion of sequences resembling the telomeric 69 bp repeats. The TP05 genome spans 196,260 bp and encodes 219 genes. The revised sequence documents the integrity of all the genes in the conserved virus core. Phylogenetic methods show that TianTan belongs to a unique clade of VACV, but probably also share a common origin with strains belonging to the Copenhagen/Lister lineage and distinct from the Wyeth/Dryvax lineage.