Genome sequence of the Myxoma virus Borghi vaccine strain

Abstract

Myxomatosis is a viral epizootic disease affecting the European rabbit (Oryctolagus cuniculus), caused by the Myxoma virus (MYXV), a member of the Poxviridae family, Chordopoxvirinae subfamily, and Leporipoxvirus genus. In this susceptible host, myxomatosis manifests in two clinical forms: the “typical” form, leading to high mortality in wild rabbit populations, and the respiratory (amyxomatous or “atypical”) form, more common in farmed rabbits.

Two geographically distinct MYXV types have been identified in the American native long-term host: South American and North American (Californian), exhibiting distinctive differences in genomic organization. Vaccination with attenuated viral strains derived from both types is used to control disease spread in endemic regions. In Italy, farmed rabbits are predominantly vaccinated with the attenuated Borghi strain, derived from the Californian MYXV-MSD strain. To characterize the Borghi vaccine strain, we sequenced its genome using next-generation sequencing (NGS) technologies, including Illumina and Oxford Nanopore platforms.

Comparison of the MYXV Borghi strain genome with the reference MYXV Lausanne strain, the prototype of European circulating strains, revealed complete deletion of 13 open reading frames (ORFs) and severe alterations or early termination in 12 additional ORFs, most encoding immunomodulatory proteins. Notably, eight of the 11 members of the large E3 ubiquitin ligase family (key for immune evasion) are completely altered. The Borghi strain also exhibits partial inverted duplication of several ORFs - M150, M151, M152, and M153 - as previously observed in the Californian MYXV-MSW strain. However, unlike the MYXV-MSW strain, the Borghi strain shows various alterations or truncations in nearly all these genes, with only M152 remaining intact. In contrast, M152 is disrupted, not deleted, in the MYXV-MSW strain. Finally, conservation of deduced immunodominant proteins validates the vaccine strain's ability to safely induce immunity and confirms its suitability for field deployment.