The complete DNA sequence of myxoma virus

Myxomatosis in European rabbits is a severely debilitating disease characte rized by profound systemic cellular immunosuppression and a high rate of mo rtality. The causative agent, myxoma virus, is a member of the poxvirus fam ily and prototype of the Leporipoxvirus genus. As a major step toward defin ing the genetic strategies by which the virus circumvents host antiviral re sponses, the genomic DNA sequence of myxoma virus, strain Lausanne, was det ermined. A total of 171 open reading frames were assigned to cover the 161. 8-kb genome, including two copies each of the 12 genes that map within the 11.5-kb terminal inverted repeats. Database searches revealed a central cor e of approximately 120 kb that encodes more than 100 genes that exhibit clo se relationships to the conserved genes of members of other poxvirus genera . Open reading frames with predicted signal sequences, localization motifs, or homology to known proteins with immunomodulatory or host-range function s were examined more extensively for predicted features such as hydrophobic regions, nucleic acid binding domains, ankyrin repeats, serpin signatures, lectin domains, and structural cysteine spacings. As a result, several nov el, potentially immunomodulatory proteins have been identified, including a family with multiple ankyrin-repeat domains, an OX-2 like member of the ne ural cell adhesion molecule family a third myxoma serpin, a putative chemok ine receptor fragment, two natural killer receptor-like species, and a vari ety of species with domains closely related to diverse host immune regulato ry proteins. Coupled with the genomic sequencing of the related leporipoxvi rus Shope fibroma virus, this work affirms the existence of a conserved com plement of poxvirus-specific core genes and expands the growing repertoire of virus genes that confer the unique capacity of each poxvirus family memb er to counter the immune responses of the infected host. (C) 1999 Academic Press.