EVIDENCE FOR RECENT GENETIC-VARIATION IN MONKEYPOX VIRUSES

DNA from isolates of monkeypox virus, when digested with the endonucle ase PstI, gave fragment-size profiles which correlated with the geogra phic area from which the isolate originated. Although some of the diff erences were located subterminally in the genome, others mapped to the central conserved region. Further differentiation of the viral genome s was sought by analysis of a short region within the central conserve d part of the genome that appeared to be a partially deleted counterpa rt of an intact 1024 bp open reading frame (ORF) present in variola an d vaccinia virus genomes. We reasoned that this region would not be co nserved by functional selection and would therefore be likely to show more variation between isolates of monkeypox virus. The deletions foun d in monkeypox virus isolates from Liberia and from Benin were almost the same as that which we had previously found in the Denmark strain. A much shortened ORF, potentially coding for a product of 133 amino ac ids, was retained in all three West African isolates, but three Zairea n isolates each showed an identical series of small insertions and del etions which effectively abolish the ORF. Three deletions, present in all isolates, must pre-date the geographical separation of monkeypox v irus lineages, other, presumably more recent, changes differ between t he Zairean and West African isolates. In contrast, the base similarity was found to be more than 99% when all the monkeypox virus sequences were appropriately aligned. This, in a disrupted and presumably nonfun ctional gene also indicates that the changes described are recent. It is suggested that insertions and deletions occur regularly during poxv irus DNA replication, but are preserved only in sequences that are not required for continued transmission in the natural host.