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item Tulman, Edan
item Delhon, Gustavo
item Afonso, Claudio
item Lu, Zhiqiang
item Zsak, Laszlo
item Kutish, Gerald
item Rock, Daniel

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/3/2006
Publication Date: 9/1/2006
Citation: Tulman, E., Delhon, G., Afonso, C.L., Lu, Z., Zsak, L., Sandybaev, N.T., Kerembekova, U.Z., Zaitsev, V.L., Kutish, G.F., Rock, D.L. 2006. Genome of horsepox virus. Journal of Virology. 80(18):9244-9258.

Interpretive Summary: This paper present the first description of the genome of Horsepox virus, a virus that cause multiple clinical forms in horses including a benign, localized form involving lesions in the muzzle and buccal cavity known previously as contagious pustular stomatitis, and a generalized, highly contagious form known as equine papular stomatitis. Comparative analysis of the horsepox genome and other poxviruses that causes disease in humans was used to identify poxviral genes with potential involvement in viral mechanisms utilized to interact with the host and to clarify the evolution of poxviruses. Poxviruses cause significant diseases in many mammalian including human, bovine, swine and avian species, among others and the genomic similarities and differences other viruses that infect humans will help understand poxviral mechanisms of replication and host interaction and may contribute to the better design of more efficient vaccines.

Technical Abstract: Here we present the genomic sequence of horsepox virus (HSPV) isolate MNR-76, an orthopoxvirus (OPV) isolated in 1976 from diseased Mongolian horses. The 212 kbp genome contained 7.5 kbp inverted terminal repeats (ITR) and lacked extensive terminal tandem repetition. HSPV contained 236 ORFs with similarity to those in other OPV, with those in the central 100 kbp most conserved relative to other OPV. Phylogenetic analysis of the conserved region indicated that HSPV is closely related to sequenced isolates of vaccinia virus (VACV) and rabbitpox virus, clearly grouping together these VACV-like viruses. Fifty-five HSPV ORFs likely represented fragments of twenty- seven orthologous OPV genes, including in the central region the only known fragmented form of an OPV ribonucleotide reductase large subunit gene. In terminal genomic regions, HSPV lacked full-length homologues of genes variably fragmented in other VACV-like viruses, but was unique in fragmentation of the homologue of VACV strain Copenhagen B6R, a gene intact in other known VACV-like viruses. Notably, HSPV contained in terminal genomic regions 17 kbp of OPV-like sequence absent in known VACV-like viruses, including fragments of genes intact in other OPV and approximately 1.2 kb of sequence present only in cowpox virus (CPXV). HSPV also contained seven full-length genes fragmented or missing in other VACV-like viruses, including intact homologues of the CPXV strain GRI-90 D2L/I4R crmB and D13L CD30-like TNFRs, D3L and C1L ankyrin-repeat proteins, B19R kelch-like protein, D7L BTB/POZ-domain protein, and B22R variola virus B22R-like protein. These results indicated that HSPV contains unique genomic features likely contributing to a unique virulence/host range phenotype. They also indicated that while closely related to known VACV, HSPV contains additional, potentially ancestral, sequences absent in other VACV-like viruses.