Abstract
Over the years, as more complete poxvirus genomes have been sequenced, phylogenetic studies of these viruses have become more prevalent. In general, the results show similar relationships between the poxvirus species; however, some inconsistencies are notable. Previous analyses of the viral genomes contained within the vaccinia virus (VACV)-Dryvax vaccine revealed that their phylogenetic relationships were sometimes clouded by low bootstrapping confidence. To analyze the VACV-Dryvax genomes in detail, a new tool-set was developed and integrated into the Base-By-Base bioinformatics software package. Analyses showed that fewer unique positions were present in each VACV-Dryvax genome than expected. A series of patterns, each containing several single nucleotide polymorphisms (SNPs) were identified that were counter to the results of the phylogenetic analysis. The VACV genomes were found to contain short DNA sequence blocks that matched more distantly related clades. Additionally, similar non-conforming SNP patterns were observed in (1) the variola virus clade; (2) some cowpox clades; and (3) VACV-CVA, the direct ancestor of VACV-MVA. Thus, traces of past recombination events are common in the various orthopoxvirus clades, including those associated with smallpox and cowpox viruses.
Highlights
The orthopoxviruses comprise one genus of the family Poxviridae; all poxviruses have a linear dsDNA genome, ranging in size from 140 to 350 kb
A variety of animal and human pathogens are present in other poxvirus genera, but the orthopoxviruses have been most studied because they include variola virus (VARV), the causative agent of the smallpox disease, and its vaccine, vaccinia virus (VACV) [4]
There are a wide variety of bioinformatics tools for comparative genomics analyses, often the presentation of the results shields the researcher from the raw data; this makes the researcher reliant on the software for correct interpretation of the data
Summary
The orthopoxviruses comprise one genus of the family Poxviridae; all poxviruses have a linear dsDNA genome, ranging in size from 140 to 350 kb. Eighty-nine genes are conserved in all Chordopoxviruses and 49 in all poxviruses; genus and species-specific genes are often located near the ends of the genome [1,2]. A variety of animal and human pathogens are present in other poxvirus genera, but the orthopoxviruses have been most studied because they include variola virus (VARV), the causative agent of the smallpox disease, and its vaccine, vaccinia virus (VACV) [4]. The first smallpox vaccine, as used by Jenner in the 1790s, is thought to have been a poxvirus isolated from cows/milkmaids; such cowpox viruses (CPXV) appear to be endemic in Eurasia, likely with small rodents as their natural reservoir. Recent genomic sequencing of a series of CPXV isolates has distinguished several clades among these viruses and suggests that VACV is more similar to CPXV strains with European ancestry [7,8]. In addition this work reported that several very similar CPXV isolates grouped with VARV and its closest relatives
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