Smallpox abstract: Analysis of nucleotide sequences of individual orthopoxvirus genes

Overview

.V. Babkin, M.V. Mikheev, S.N. Shchelkunov, and L.S. Sandakhchiev
State Research Center of Virology and Biotechnology Vector, Koltsovo, Novosibirsk oblast, 630559 Russia

The evolutionary relationships of various orthopoxvirus species are far from being clarified. From this standpoint, it is interesting to compare organizations of various orthopoxvirus genes to find out whether the genes evolve independently of one another or there are general patterns of their changes.

The goal of this work was to determine nucleotide sequences of the genes determining virulence of orthopoxviruses and structural genes and perform their computer analysis.

The nucleotide sequences of genes encoding important virulence factors, such as viral growth factor, γ-interferon receptor, receptor of α/β-interferons, and receptor of chemokines as well as 14K fusion protein and hemagglutinin were analyzed. The nucleotide sequences of the genes studied were aligned to analyze their phylogeny.

Analysis of the nucleotide sequences in question of these genes demonstrated that these genes in their phylogenetic relationships cluster, as a rule, according to their species attribution with the only exception of cowpox virus. This virus forms several subclusters that are considerably distant from one another. These results are a confirmation of the hypothesis that cowpox or cowpox-like virus was the ancestor of all the modern orthopoxviruses.

Comparison of the dendrograms constructed detects several common features. Relatedness of variola and camelpox viruses, which, according to earlier data, have a common ancestor, was demonstrated. The clade of variola virus, as a rule, fall into two subclades—variola major and alastrim. Interestingly, no distinctions were found between the nucleotide sequences of viral genes isolated from human scabs and those passaged in cell cultures. In the case of chemokine-binding protein, three subclades were found, formed by the strains coming from different geographic regions.

The clade of monkeypox viruses display two subclades represented by the strains isolated in Central Africa, on the one hand, and strains isolated in West Africa, on the other. In addition, in the case of chemokine receptor, viral growth factor, and hemagglutinin, the monkeypox virus strains isolated earlier differ from the samples isolated recently. This fact is interesting in the view of recent increase in monkeypox virus contagiousness.

An important result of this study is the fact that when comparing different individual genes, phylogenetic relationships between the same orthopoxviruses may differ. Presumably, this suggests that different species of orthopoxviruses during their evolution may exchange fragments of their genomes.

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