Genome of deerpox virus

Abstract

Deerpox virus (DPV), an uncharacterized and unclassified member of the Poxviridae, has been isolated from North American free-ranging mule deer (Odocoileus hemionus) exhibiting mucocutaneous disease. Here we report the genomic sequence and comparative analysis of two pathogenic DPV isolates, W-848-83 (W83) and W-1170-84 (W84). The W83 and W84 genomes are 166 and 170 kbp, containing 169 and 170 putative genes, respectively. Nucleotide identity between DPVs is 95% over the central 157 kbp. W83 and W84 share similar gene orders and code for similar replicative, structural, virulence, and host range functions. DPV open reading frames (ORFs) with putative virulence and host range functions include those similar to cytokine receptors (R), including gamma interferon receptor (IFN-gammaR), interleukin 1 receptor (IL-1R), and type 8 CC-chemokine receptors; cytokine binding proteins (BP), including IL-18BP, IFN-alpha/betaBP, and tumor necrosis factor binding protein (TNFBP); serpins; and homologues of vaccinia virus (VACV) E3L, K3L, and A52R proteins. DPVs also encode distinct forms of major histocompatibility complex class I, C-type lectin-like protein, and transforming growth factor beta1 (TGF-beta1), a protein not previously described in a mammalian chordopoxvirus. Notably, DPV encodes homologues of cellular endothelin 2 and IL-1R antagonist, novel poxviral genes also likely involved in the manipulation of host responses. W83 and W84 differ from each other by the presence or absence of five ORFs. Specifically, homologues of a CD30 TNFR family protein, swinepox virus SPV019, and VACV E11L core protein are absent in W83, and homologues of TGF-beta1 and lumpy skin disease virus LSDV023 are absent in W84. Phylogenetic analysis indicates that DPVs are genetically distinct from viruses of other characterized poxviral genera and that they likely comprise a new genus within the subfamily Chordopoxvirinae.

FIG. 1.

Multiple amino acid alignment of DPV006 with endothelins and DPV054 with secreted IL-1Ra (isoform 1). Amino acid positions are indicated on the right; / indicates truncation of the amino acid sequence, * indicates residues critical for receptor binding, and ^ indicates cleavage sites. (A) Alignment of DPV006 to endothelin homologues. ET peptide is underlined. Accession numbers are the following: P22389, mouse; P23943, rat; P12064, dog; and P20800, human. (B) Alignment of DPV054 to IL-1Ra. Accession numbers are the following: AB038268, dolphin; L38849, pig; AB005148, cow; P18510, human; AY026462, dog; P26890, rabbit; and P25086, rat.

FIG. 2.

Phylogenetic analysis of DPV proteins. Seventy-nine conserved ORFs between DPV039 and DPV125 were concatenated from W83 and W84 and aligned with similarly concatenated ORF sets from other ChPVs with DIALIGN. Unrooted trees were generated by neighbor-joining analysis with Poisson correction for multiple substitutions and 500 bootstrap replicates as implemented in PHYLO_WIN (A) and maximum likelihood analysis with JTT correction for multiple substitutions and 1,000 quartet puzzling steps as implemented in TREE-PUZZLE (B). Bootstrap (A) or support (B) values of 100% are marked with dots; values less than 100% are presented at appropriate nodes. Homologous protein sequences from the following viruses and accession numbers were compared: bovine popular stomatitis virus (BPSV), AY386265; canarypox virus (CNPV), AY318871; ectromelia virus (ECTV), AF012825; fowlpox virus (FWPV), AF198100; lumpy skin disease virus (LSDV), AF325528; molluscum contagiosum virus (MOCV), MCU60315; myxoma virus (MYXV), AF170726; orf virus (ORFV), AY386264; rabbit (Shope) fibroma virus (SFV), AF170722; sheeppox virus (SPPV), AY077833; swinepox virus (SWPV), AF410153; vaccinia virus (VACV), M35027; Yaba-like disease virus (YLDV), AJ293568; and Yaba monkey tumor virus (YMTV), AY386371. Similar results were obtained by using an alignment manually edited to include only unambiguously aligned sites (20,132 of 30,019 sites) and using alignments generated with CLUSTAL W (data not shown).