DNA sequence variation as a clue to the phylogenesis of orthopoxviruses

Abstract

We have sequenced DNA equivalent to the E5R ORF of Copenhagen vaccinia virus from an additional strain of vaccinia and from cowpox (three strains), camelpox (two strains), taterapox and ectromelia viruses. None of these showed the disruptions previously reported in the equivalent region of monkeypox virus. We also constructed a viable recombinant of vaccinia virus strain Dairen in which the E5R sequence was disrupted by a 436 bp deletion and substitution of the E. coli gpt gene. Quantitative analysis of the sequences, including available sequences from monkeypox, variola and vaccinia viruses revealed four main groupings, namely cowpox, ectromelia, monkeypox and a cluster which includes variola, camelpox, taterapox and vaccinia viruses. It was noted that, at over 75% of the positions which differentiated species, all species but one had a common nucleotide. Although the analysis covers one single gene only, the results accord with what is known of the biology of the viruses.

The sequence of camelpox virus shows it is most closely related to variola virus, the cause of smallpox

“…Collectively, the phylogenetic analysis of proteins showed VAR and CMPV are most closely related, consistent with analysis of two CMPV genes (Binns, 1992 ;Douglass & Dumbell, 1996), which showed CMPV, VAR and taterapoxvirus are closely related.…”

Role of viruses in human evolution

“…It infects only humans, however, so its source is unclear. Its closest relatives are camelpox, gerbilpox, and monkeypox, the latter maintained in a rodent reservoir, in spite of its name (Douglas and Dumbell, 1996). Figure 6 shows some likely relationships among members of this family, but these ultimately depend on where in the genome one looks (Blasco, 1995).…”

“…RNA viruses thus have a frightening ability to evolve and adapt to new hosts, and also to increase in virulence. They are less species-specific Blasco (1995), Douglas and Dumbell (1996), and Senkevich et al (1997). Viruses specifically adapted to humans are indicated by bold and italicized capitals.…”

Human monkeypox and smallpox viruses: genomic comparison

“…The major and minor subspecies of VAR are closely related to each other and MPV seems slightly more distant from VAR than VAC. Camelpox and taterapox viruses appear closer to VAR based on a comparison of short DNA sequences [41]. CPV may be nearest to the progenitor orthopoxvirus, as it contains all genes collectively present in the other members of this genus [17].…”

“…In addition, the clinical similarities of human monkeypox and smallpox raised questions regarding the genetic relationships of the viruses and whether MPV could evolve into a VAR‐like virus with a high frequency of human‐to‐human transmission [5,7,8]. Although some preliminary genetic information indicating differences between VAR, MPV and other orthopoxviruses was obtained by comparative analysis of restriction endonuclease site maps and short DNA sequences [6,9–12], less than 7% of the MPV genome sequence was in GenBank prior to this study. To provide a definitive comparison of MPV and VAR, the DNA of MPV strain Zaire‐96‐I‐16 (MPV‐ZAI), isolated during the 1996 outbreak of human monkeypox in Zaire [6] was sequenced.…”