Abstract
Multiple repeats of the ankyrin motif (ANK) are ubiquitous throughout the kingdoms of life but are absent from most viruses. The main exception to this is the poxvirus family, and specifically the chordopoxviruses, with ANK repeat proteins present in all but three species from separate genera. The poxviral ANK repeat proteins belong to distinct orthologue groups spread over different species, and align well with the phylogeny of their genera. This distribution throughout the chordopoxviruses indicates these proteins were present in an ancestral vertebrate poxvirus, and have since undergone numerous duplication events. Most poxviral ANK repeat proteins contain an unusual topology of multiple ANK motifs starting at the N-terminus with a C-terminal poxviral homologue of the cellular F-box enabling interaction with the cellular SCF ubiquitin ligase complex. The subtle variations between ANK repeat proteins of individual poxviruses suggest an array of different substrates may be bound by these protein-protein interaction domains and, via the F-box, potentially directed to cellular ubiquitination pathways and possible degradation. Known interaction partners of several of these proteins indicate that the NF-κB coordinated anti-viral response is a key target, whilst some poxviral ANK repeat domains also have an F-box independent affect on viral host-range.
Highlights
Multiple repeats of the ankyrin motif (ANK) are ubiquitous throughout the kingdoms of life but are absent from most viruses
The poxviral ANK/F-box proteins demonstrate a number of conserved features that indicate a shared evolutionary background and role
Poxviral genomes that encode ANK repeat proteins demonstrate a maintenance of a minimal number of ankyrin proteins localised to the terminal regions of the genome, a frequently conserved synteny of these genes between genera, and a segregation into distinct orthologue groups due to gene duplication within and between genera
Summary
Poxviruses are nucleocytoplasmic large DNA viruses (NCLDV) [1,2] that replicate exclusively in the cytoplasm and maintain genomes of 130 to >350 kilobases. The terminal regions of the linear poxviral genome introduce a significant variation between poxviral species and are replete with a wide range of genus- or species-specific genes. Proteins expressed from these terminal regions frequently determine host-range and significantly contribute to infection and virulence by successfully interfering with the cellular and immune response to viral presence [17,18,19,20]. ANK repeat proteins are absent from the known species of Molluscipoxvirus, Crocodylidpoxvirus and the red squirrel poxvirus [34,40,41,42,43] and from all the known Entomopoxvirus genera [44,45,46]
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