Ellena M Whelan

University of Otago , Taieri, Otago Region, New Zealand

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Publications (4)14.24 Total impact

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    ABSTRACT: Vaccines based on recombinant poxviruses have proved successful in controlling diseases such as rabies and plague in wild eutherian mammals. They have also been trialled experimentally as delivery agents for fertility-control vaccines in rodents and foxes. In some countries, marsupial mammals represent a wildlife disease reservoir or a threat to conservation values but, as yet there has been no bespoke study of efficacy or immunogenicity of a poxvirus-based vaccine delivery system in a marsupial. Here, we report a study of the potential for vaccination using vaccinia virus in the Australian brushtail possum Trichosurus vulpecula, an introduced pest species in New Zealand. Parent-strain vaccinia virus (Lister) infected 8/8 possums following delivery of virus to the oral cavity and outer nares surfaces (oronasal immunisation), and persisted in the mucosal epithelium around the palatine tonsils for up to 2 weeks post-exposure. A recombinant vaccinia virus construct (VV399, which expresses the Eg95 antigen of the hydatid disease parasite Echinococcus granulosus) was shown to infect 10/15 possums after a single-dose oronasal delivery and to also persist. Both parent vaccinia virus and the VV399 construct virus induced peripheral blood lymphocyte reactivity against viral antigens in possums, first apparent at 4 weeks post-exposure and still detectable at 4 months post-exposure. Serum antibody reactivity to Eg95 was recorded in 7/8 possums which received a single dose of the VV399 construct and 7/7 animals which received triple-dose delivery, with titre end-points in the latter case exceeding 1/4000 dilution. This study demonstrates that vaccinia virus will readily infect possums via a delivery means used to deploy wildlife vaccines, and in doing is capable of generating immune reactivity against viral and heterologous antigens. This highlights the future potential of recombinant vaccinia virus as a vaccine delivery system in marsupial wildlife.
    Vaccine 06/2011; 29(28):4537-43. · 3.49 Impact Factor
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    ABSTRACT: Orf virus infection causes a contagious pustular dermatitis characterized by extensive vascular changes that have been linked to a virally encoded vascular endothelial growth factor (VEGF). The VEGF genes of different strains of orf virus can vary extensively in amino acid sequence. Functional analyses of two major variant VEGF proteins derived from orf virus strains, NZ2 and NZ7, have revealed quantitative differences in biological activities and receptor binding specificities suggesting that these viral VEGFs could have different roles in the pathology of orf virus infection. In this study, we show that both orf virus strains express equivalent levels of the viral VEGF variants and during infection of sheep skin induce comparable levels of vascularization, edema, epidermal rete ridge and scab formation. Recombinants of orf virus NZ2 and NZ7 strains in which the variant VEGF genes were disrupted showed markedly reduced vascular changes and evidence of partially attenuated viral growth. These results demonstrate that despite substantial differences in sequence and biological activity in vitro, these virally expressed virulence factors are functionally equivalent in their natural host, contributing equally to orf virus pathology.
    Virus Research 10/2007; 128(1-2):115-25. · 2.83 Impact Factor
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    ABSTRACT: Apoptotic cell death forms part of the host defense against virus infection. We tested orf virus, a member of the poxvirus family, for the ability to inhibit apoptosis and found that orf virus-infected cells were fully resistant to UV-induced changes in cell morphology, caspase activation, and DNA fragmentation. By using a library of vaccinia virus-orf virus recombinants, we identified an orf virus gene (ORFV125) whose presence was linked with the inhibition of apoptosis. The 173-amino-acid predicted protein had no clear homologs in public databases other than those encoded by other parapoxviruses. However, ORFV125 possessed a distinctive C-terminal domain which was necessary and sufficient to direct the protein to the mitochondria. We determined that ORFV125 alone could fully inhibit UV-induced DNA fragmentation, caspase activation, and cytochrome c release and that its mitochondrial localization was required for its antiapoptotic function. In contrast, ORFV125 did not prevent UV-induced activation of c-Jun NH2-terminal kinase, an event occurring upstream of the mitochondria. These features are comparable to the antiapoptotic properties of the mitochondrial regulator Bcl-2. Furthermore, bioinformatic analyses revealed sequence and secondary-structure similarities to Bcl-2 family members, including characteristic residues of all four Bcl-2 homology domains. Consistent with this, the viral protein inhibited the UV-induced activation of the proapoptotic Bcl-2 family members Bax and Bak. ORFV125 is the first parapoxvirus apoptosis inhibitor to be identified, and we propose that it is a new antiapoptotic member of the Bcl-2 family.
    Journal of Virology 08/2007; 81(13):7178-88. · 4.65 Impact Factor
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    ABSTRACT: The large differences between the G+C content of the orf virus genome and those of other characterized poxviruses have precluded the use of DNA hybridization to establish a gene map of orf virus. Here we have sequenced the ends of cloned restriction endonuclease fragments of the nZ2 strain of orf virus (OV) and used the translated sequences to search protein data bases. Sequence from 15 points found high-scoring matches to data base entries, including 18 vaccinia virus (VAC) genes. We also present 2 kb of sequence from a region near the right terminus of the OV genome and show that it encodes homologs of VAC genes, F9L and F10L. The data presented here in conjunction with published and as yet unpublished data have allowed the construction of a gene map of OV on which 37 genes have been placed. Thirty-two of these genes have homologs in VAC. Alignment of the OV gene map with that of VAC revealed that each OV gene and its VAC counterpart occurred in the same order and orientation on their respective genomes. The intervals between many of the points of sequence were also found to be strikingly similar. The conserved spacing of genes between OV and VAC within the central 88.2 kb of the 139-kb OV genome is not maintained in the termini where insertion, deletion, and translocation have occurred. Parallels are drawn between the data presented here and related data from swinepox virus and capripox virus.
    Virology 11/1995; 212(2):698-704. · 3.28 Impact Factor