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Title: GENOME OF CROCODILEPOX VIRUS

Author
item Afonso, Claudio
item TULMAN, E - PLUM ISL DIS CTR-NEW YORK
item DELHON, G - PLUM ISL DIS CTR-NEW YORK
item LU, Z - PLUM ISL DIS CTR-NEW YORK
item VILJOEN, G - IAEA-VIENNA, AUSTRIA
item WALLACE, D - ONDERSTEPOORT-SO. AFRICA
item KUTISH, G - PLUM ISL DIS CTR-NEW YORK
item ROCK, D - PLUM ISL DIS CTR-NEW YORK

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2006
Publication Date: 5/1/2006
Citation: Afonso, C.L., Tulman, E.R., Delhon, G., Lu, Z., Viljoen, G.J., Wallace, D.B., Kutish, G.F., Rock, D.L. 2006. Genome of crocodilepox virus. Journal of Virology. 80(10)4978-4991.

Interpretive Summary: Here we present the genome sequence, with analysis, of a poxvirus infecting Nile crocodiles (Crocodylus niloticus) (CRV). Comparative analysis of the CRV genome and other poxviruses was used to identify poxviral genes with potential involvement in viral mechanisms utilized by poxviruses to interact with the host, and genomic information was used to clarify the evolution of poxviruses. Poxviruses cause significant diseases in mammalians including human, bovine, swine and avian species, among others. CRV is the first poxvirus of a reptile to be studied, and the representative of a new poxviral genus, and the differences between the genome of CRV and other ChPVs are notable. CRV shares notable genomic similarities with molluscum contagiosum virus, that infect humans, including ORFs found only in these two viruses. Novel genes present in CRV likely encode proteins involved in manipulation of the host. Comparative analysis of CRV and other poxviruses will help understand poxviral mechanisms of replication and host interaction and may contribute to better designing more efficient vaccines.

Technical Abstract: Here we present the genome sequence, with analysis, of a poxvirus infecting Nile crocodiles (Crocodylus niloticus) (CRV). The genome is 190054 bp (62% G+C) and encodes 173 open reading frames (ORFs) of 53 to 1941 amino acids. The central genomic region contains genes conserved and generally colinear with those of other chordopoxviruses (ChPV). CRV is distinct, as the terminal 33kbp (left) and 13kbp (right) genomic regions are largely CRV specific, containing forty-eight unique ORFs which lack similarity to other poxviral genes. Notably, CRV also contains 14 unique ORFs which disrupt ChPV gene colinearity within the central genomic region, including seven ORFs containing GyrB-like ATPase domains similar to those in cellular type IIA DNA topoisomerases suggestive of novel ATP-dependent functions. The presence of ten CRV ORFs with similarity to components of cellular multisubunit E3 ubiquitin-protein ligase complexes, including nine ORFs containing F-box motifs and F-box associated regions and a homologue of cellular anaphase promoting complex subunit 11 (Apc11), suggests that modification of host ubiquitination pathways may be significant for CRV-host cell interaction. CRV contains a novel complement of genes potentially involved in DNA replication, including a NAD+ dependent DNA ligase, an ORF with similarity to both VACV F16L and prokaryotic serine site-specific resolvase-invertases, and a lack of genes involved in nucleotide metabolism. CRV shares notable genomic similarities with molluscum contagiosum virus, including ORFs found only in these two viruses. Phylogenetic analysis indicates that CRV is quite distinct from other ChPV, representing a new genus within the subfamily, and it lacks recognizable homologues of most ChPV genes involved in virulence and host range, including those involving interferon response, intracellular signaling, and host immune response modulation. These data reveal the unique nature of CRV and suggest mechanisms of virus-reptile host interaction.