Variola virus genomics
J.J. Esposito, S. Sammons, M. Frace, Y. Li, M. Olsen-Rasmussen, M. Zhang, J. Osborne, M. Laker, R. Kline, I.K. Damon, J. LeDuc, R.M. Wohlhueter
Centers for Disease Control and Prevention, Atlanta, United States
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The genomes of 8 variola strains, chosen by systematically by reducing the approximately 400 variola virus specimens in the repository at CDC to a sample size of 45 strains, mainly on epidemiological criteria, were selected by correlating the 45 strains by restriction fragment length polymorphism (RFLP) cluster analysis. The RFLP assays, which should be useful for comparatively screening for differences in entire genomes, and the sequencing templates essentially used sets of 20 PCR amplicons designed to overlap to virtually span each selected viral DNA genome.
The sequences showed that the coding regions of the 8 strains were rather alike, containing about 200 predicted genes or gene vestiges of which under half were identical and the majority encoded for proteins whose counterparts had at least amino acid difference. The similarity of predicted proteins of the newly sequenced variola viruses and two prior published strains suggest that a diverse battery of test probes and antivirals should be unnecessary to verify a clinical diagnosis and treat smallpox if it reappears, and antigenic variation should not be a major issue for future vaccine design. More, the sequences and variations observed should help improve diagnostic and forensic tests, targeting antivirals, and understanding pathogenesis mechanisms and putative animal models.