Andrew A Mercer

University of Otago , Taieri, Otago Region, New Zealand

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Publications (87)322.79 Total impact

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    ABSTRACT: Expression of numerous chemokine-related genes is increased in the brain after ischemic stroke. Here, we tested whether post-stroke administration of a chemokine-binding protein (CBP), derived from the parapoxvirus bovine papular stomatitis virus, might reduce infiltration of leukocytes into the brain and consequently limit infarct development. The binding spectrum of the CBP was evaluated in chemokine ELISAs, and binding affinity was determined using surface plasmon resonance. Focal stroke was induced in C57Bl/6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion for 23 or 47 hours. Mice were treated intravenously with either bovine serum albumin (10 μg) or CBP (10 μg) at the commencement of reperfusion. At 24 or 48 hours, we assessed plasma levels of the chemokines CCL2/MCP-1 and CXCL2/MIP-2, as well as neurological deficit, brain leukocyte infiltration, and infarct volume. The CBP interacted with a broad spectrum of CC, CXC, and XC chemokines and bound CCL2/MCP-1 and CXCL2/MIP-2 with high affinity (pM range). Stroke markedly increased plasma levels of CCL2/MCP-1 and CXCL2/MIP-2, as well as numbers of microglia and infiltrating leukocytes in the brain. Increases in plasma chemokines were blocked in mice treated with CBP, in which there was reduced neurological deficit, fewer brain-infiltrating leukocytes, and ≈50% smaller infarcts at 24 hours compared with bovine serum albumin-treated mice. However, CBP treatment was no longer protective at 48 hours. Post-stroke administration of CBP can reduce plasma chemokine levels in association with temporary attenuation of brain inflammation and infarct volume development. © 2014 American Heart Association, Inc.
    Stroke 12/2014; · 6.02 Impact Factor
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    ABSTRACT: Interleukin (IL)-10 plays a critical role in controlling wound inflammation and scar formation. Orf virus, a zoonotic parapoxvirus, induces proliferative skin lesions that resolve with minimal scarring. Orf virus encodes a range of factors that subvert the host's response to infection, including a homolog of IL-10. This study investigated, using a murine full-thickness wound model, whether purified orf virus IL-10 (ovIL-10) can regulate skin repair and scarring. Repeat injections of ovIL-10 into wounded skin accelerated wound closure. Histological analyses of wound sections revealed that treatment with ovIL-10 accelerated wound reepithelialization, granulation tissue coverage of the wound bed, and improved wound revascularization. In addition, wounds treated with ovIL-10 showed a reduction in macrophage infiltration, myofibroblast differentiation, and wound contraction. Treatment of wounds with ovIL-10 also resulted in a reduction in visible scarring that was consistent with the extent of scar tissue formed. Quantitative polymerase chain reaction analysis confirmed that ovIL-10 reduced the expression of key mediators of inflammation and granulation tissue formation. These findings show that ovIL-10, like mammalian IL-10, limits inflammation and scar tissue formation and reveal a new role for both mammalian and viral IL-10 in mediating tissue repair.
    Wound Repair and Regeneration 05/2014; 22(3). · 2.77 Impact Factor
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    ABSTRACT: Inactivated orf virus (iORFV), strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV) and hepatitis B virus (HBV). Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.
    PLoS ONE 01/2013; 8(9):e74605. · 3.53 Impact Factor
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    ABSTRACT: There is increasing evidence supporting DNA virus regulation of the cell adhesion and tumour suppressor protein, E-cadherin. We previously reported that loss of E-cadherin in human papillomavirus (HPV) type 16-infected epidermis is contributed to by the major viral proto-oncogene E6 and is associated with reduced Langerhans cells density, potentially regulating the immune response. The focus of this study is determining how the HPV16 E6 protein mediates E-cadherin repression. We found that the E-cadherin promoter is repressed in cells expressing E6, resulting in fewer E-cadherin transcripts. On exploring the mechanism for this, repression by increased histone deacetylase activity or by increased binding of trans-repressors to the E-cadherin promoter Epal element was discounted. In contrast, DNA methyltransferase (DNMT) activity was increased in E6 expressing cells. Upon inhibiting DNMT activity using 5-Aza-2'-deoxycytidine, E-cadherin transcription was restored in the presence of HPV16 E6. The E-cadherin promoter was not directly methylated, however a mutational analysis showed general promoter repression and reduced binding of the transactivators Sp1 and AML1 and the repressor Slug. Expression of E7 with E6 resulted in a further reduction in surface E-cadherin levels. This is the first report of HPV16 E6-mediated transcriptional repression of this adhesion molecule and tumour suppressor protein.
    PLoS ONE 11/2012; 7(11):e48954. · 3.53 Impact Factor
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    ABSTRACT: Viruses can manipulate the immune response against them by various strategies to influence immune cells, i.e. by over-activation leading to functional inactivation, bypassing antigen presentation or even suppression of effector functions. Little is known, however, about how these features of immune regulation and modulation could be used for therapeutic purposes. Reasons for this include the complexity of immune regulatory mechanisms under certain disease conditions and the risks that infections with viruses pose to human beings. The orf virus (ORFV), a member of the Parapoxvirus genus of the poxvirus family, is known as a common pathogen in sheep and goats worldwide. The inactivated ORFV, however, has been used as a preventative as well as therapeutic immunomodulator in veterinary medicine in different species. Here, we review the key results obtained in pre-clinical studies or clinical studies in veterinary medicine to characterise the therapeutic potential of inactivated ORFV. Inactivated ORFV has strong effects on cytokine secretion in mice and human immune cells, leading to an auto-regulated loop of initial up-regulation of inflammatory and Th1-related cytokines, followed by Th2-related cytokines that attenuate immunopathology. The therapeutic potential of inactivated ORFV has been recognised in several difficult-to-treat disease areas, such as chronic viral diseases, liver fibrosis or various forms of cancer. Further research will be required in order to evaluate the full beneficial potential of inactivated ORFV for therapeutic immunomodulation.
    European Journal of Clinical Microbiology 11/2012; · 3.02 Impact Factor
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    ABSTRACT: Viruses frequently exploit host cell cycle machineries for their own benefit, often by targeting 'master switches' of cell cycle regulation. By doing so, they achieve maximum effect from minimal input. One such master switch is the anaphase promoting complex or cyclosome (APC/C), a multicomponent ubiquitin ligase and a dominant regulator of the cell cycle. A growing number of viruses have been shown to target the APC/C. Although differing strategies are employed, viral manipulation of the APC/C seems to serve a common purpose, namely, to create an environment supportive of viral replication. Here, the molecular mechanisms employed by these viruses are summarized and discussed.
    Trends in Microbiology 06/2012; 20(9):440-8. · 9.81 Impact Factor
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    ABSTRACT: Vascular endothelial growth factor (VEGF)-A, a key regulator of cutaneous blood vessel formation, appears to have an additional role during wound healing, enhancing re-epithelialization. Orf virus, a zoonotic parapoxvirus, induces proliferative skin lesions that initiate in wounds and are characterized by extensive blood vessel formation, epidermal hyperplasia and rete ridge formation. The vascular changes beneath the lesion are largely due to viral-expressed VEGF-E. This study investigated using mouse skin models whether VEGF-E can induce epidermal changes such as that seen in the viral lesion. Injection of VEGF-E into normal skin increased the number of endothelial cells and blood vessels within the dermis and increased epidermal thickening and keratinocyte number. Injection of VEGF-E into wounded skin, which more closely mimics orf virus lesions, increased neo-epidermal thickness and area, promoted rete ridge formation, and enhanced wound re-epithelialization. Quantitative RT-PCR analysis showed that VEGF-E did not induce expression of epidermal-specific growth factors within the wound, but did increase matrix metalloproteinase (MMP)-2 and MMP-9 expression. In cell-based assays, VEGF-E induced keratinocyte migration and proliferation, responses that were inhibited by a neutralizing antibody against VEGF receptor (VEGFR)-2. These findings demonstrate that VEGF-E, both directly and indirectly, regulates keratinocyte function, thereby promoting epidermal regeneration.
    Cellular Microbiology 04/2012; 14(9):1376-90. · 4.82 Impact Factor
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    ABSTRACT: The tapeworm Echinococcus granulosus is the causative agent of hydatid disease and affects sheep, cattle, dogs and humans worldwide. It has a two-stage life cycle existing as worms in the gut of infected dogs (definitive host) and as cysts in herbivores and humans (intermediate host). The disease is debilitating and can be life threatening where the cysts interfere with organ function. Interruption of the hydatid life cycle in the intermediate host by vaccination may be a way to control the disease, and a protective oncosphere antigen EG95 has been shown to protect animals against challenge with E. granulosus eggs. We explored the use of recombinant vaccinia virus as a delivery vehicle for EG95. Mice and sheep were immunized with the recombinant vector, and the result monitored at the circulating antibody level. In addition, sera from immunized mice were assayed for the ability to kill E. granulosus oncospheres in vitro. Mice immunized once intranasally developed effective oncosphere-killing antibody by day 42 post-infection. Antibody responses and oncosphere killing were correlated and were significantly enhanced by boosting mice with either EG95 protein or recombinant vector. Sheep antibody responses to the recombinant vector or to EG95 protein mirrored those in mice.
    Parasite Immunology 03/2012; 34(6):312-7. · 1.85 Impact Factor
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    ABSTRACT: Replicating viruses for the treatment of cancer have a number of advantages over traditional therapeutic modalities. They are highly targeted, self-amplifying, and have the added potential to act as both gene-therapy delivery vehicles and oncolytic agents. Parapoxvirus ovis or Orf virus (ORFV) is the prototypic species of the Parapoxvirus genus, causing a benign disease in its natural ungulate host. ORFV possesses a number of unique properties that make it an ideal viral backbone for the development of a cancer therapeutic: it is safe in humans, has the ability to cause repeat infections even in the presence of antibody, and it induces a potent T(h)-1-dominated immune response. Here, we show that live replicating ORFV induces an antitumor immune response in multiple syngeneic mouse models of cancer that is mediated largely by the potent activation of both cytokine-secreting, and tumoricidal natural killer (NK) cells. We have also highlighted the clinical potential of the virus by demonstration of human cancer cell oncolysis including efficacy in an A549 xenograft model of cancer.
    Molecular Therapy 01/2012; 20(6):1148-57. · 6.43 Impact Factor
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    ABSTRACT: The parapoxvirus, orf virus (ORFV) causes superficial skin lesions in infected sheep. Unattenuated ORFV is used globally to vaccinate against orf. Recombinant poxviruses are proven delivery systems and we investigated strategies to express the immunogenic Echinococcus granulosus peptide EG95 from ORFV with the aim of developing a recombinant bivalent vaccine. EG95 is an oncosphere protein of the cestode E. granulosus, a parasite responsible for causing cystic hydatid disease in a wide range of hosts including humans and grazing animals such as sheep. Recombinant viruses were produced in which EG95 was expressed by itself or fused to ORFV envelope-associated structural proteins 10 kDa and F1L. Infection studies in sheep showed that specific antibodies were produced against ORFV and EG95 and that the antibody levels against EG95 were comparable to that of animals immunized with purified EG95 in Quil A adjuvant, an immunization regime that is known to afford protection. A single exposure to the dual vaccine has potential for protecting lambs against orf and for priming against EG95 so as to respond strongly to a later injection of EG95 protein.
    Vaccine 11/2011; 30(2):398-406. · 3.49 Impact Factor
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    ABSTRACT: Ankyrin-repeat (ANK) protein-interaction domains are common in cellular proteins but are relatively rare in viruses. Chordopoxviruses, however, encode a large number of ANK domain-containing ORFs of largely unknown function. Recently, a second protein-interaction domain, an F-box-like motif, was identified in several poxvirus ANK proteins. Cellular F-box proteins recruit substrates to the ubiquitination machinery of the cell, a putative function for ANK/poxviral F-box proteins. Using publicly available genome sequence data we examined all 328 predicted ANK proteins encoded by 27 chordopoxviruses that represented the eight vertebrate poxvirus genera whose members encode ANK proteins. Within these we identified 15 putative ANK protein orthologue groups within orthopoxviruses, five within parapoxviruses, 23 within avipoxviruses and seven across members of the genera Leporipoxvirus, Capripoxvirus, Yatapoxvirus, Suipoxvirus and Cervidpoxvirus. Sequence comparisons showed that members of each of these four clusters of orthologues were not closely related to members of any of the other clusters. Of these ORFs, 67% encoded a C-terminal poxviral F-box-like motif, whose absence could largely be attributed to fragmentation of ORFs. Our findings suggest that the large family of poxvirus ANK proteins arose by extensive gene duplication and divergence that occurred independently in four major genus-based groups after the groups diverged from each other. It seems likely that the ancestor ANK proteins of poxviruses contained both the N-terminal ANK repeats and a C-terminal F-box-like domain, with the latter domain subsequently being lost in a small subset of these proteins.
    Journal of General Virology 07/2011; 92(Pt 11):2596-607. · 3.53 Impact Factor
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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: Inactivated orf virus (ORFV, parapoxvirus ovis) induces antiviral activity in animal models of acute and chronic viral infections and exerts strong effects on human immune cells. ORFV activates antigen presenting cells (APC) via CD14 and, probably, Toll-like receptor signalling, and triggers the release of IFN-γ that has been identified as the key mediator of the antiviral activity. After delineating virus proteins as being the most likely active constituent, we aimed to characterize the ORFV proteins responsible for the therapeutic effect. By using a vaccinia virus/ORFV expression library we identified several multi-gene DNA fragments with strong immunomodulatory activity. Together these fragments contain 27 ORFs. The encoded proteins are related to virion structure and transcription but are otherwise unrelated. Two proteins were separately expressed and purified, and demonstrated immunostimulatory activity. Gene expression profiles induced by ORFV and the identified fragments were investigated by microarray analysis. Interestingly, all active fragments induced a similar gene-expression pattern, differing only in quantitative aspects. Obviously, several proteins of ORFV activate similar cellular pathways, modulating APC to generate a strong T-helper 1-dominated immune response. This was balanced by additional induction of immune dampening mechanisms, suggesting regulatory differences compared to single cytokine therapies. We conclude that ORFV may have the potential to enrich the armamentarium of antiviral therapies.
    Journal of General Virology 02/2011; 92(Pt 7):1571-84. · 3.53 Impact Factor
  • Min Mo, Stephen B Fleming, Andrew A Mercer
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    ABSTRACT: The poxvirus anaphase promoting complex regulator (PACR) promotes viral replication by manipulating the anaphase promoting complex/cyclosome (APC/C), a multisubunit ubiquitin ligase complex with essential roles in cell cycle regulation. PACR has sequence similarities to APC/C subunit 11 (APC11) and associates with APC/C subunits. However, unlike APC11, expression of PACR disrupts APC/C functions. Here, we further investigated the interaction of PACR with APC/C. Following knockdown of APC1, the subunit linking APC11/APC2 to the rest of APC/C, PACR remained bound to APC2 but not to other, distal, subunits of the complex, suggesting PACR associates with APC/C via APC2. This was supported by the demonstration, in vitro, of a direct interaction between PACR and APC2. Moreover, the presence of PACR interfered with interactions between both APC11 and APC2. Based on these observations we propose that PACR competes with APC11 for the incorporation into APC/C.
    Journal of General Virology 12/2010; 91(Pt 12):3010-5. · 3.53 Impact Factor
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    ABSTRACT: The parapoxvirus orf virus (ORFV) encodes a chemokine-binding protein (CBP) that functions to downregulate the host's immune response at the site of infection by blocking the chemokine-induced recruitment of immune cells. In order to shed light on the structural determinants of CBP-chemokine binding, ORFV CBP was crystallized as part of an ongoing structure-function study on this protein. ORFV CBP crystals were obtained by the sitting-drop vapour-diffusion technique using ammonium citrate as a precipitant. The crystal quality was greatly improved through the addition of small-molecule additives to the crystallization mother liquor. ORFV CBP crystals diffracted X-rays to 2.50 A resolution and belonged to the hexagonal space group P6(1)22 or its enantiomorph P6(5)22, with unit-cell parameters a = b = 75.62, c = 282.49 A, alpha = 90, beta = 90, gamma = 120 degrees.
    Acta Crystallographica Section F Structural Biology and Crystallization Communications 07/2010; 66(Pt 7):819-23. · 0.57 Impact Factor
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    ABSTRACT: Parapoxviruses (PPV), of the family Poxviridae, cause a pustular cutaneous disease in sheep and goats (orf virus, ORFV) and cattle (pseudocowpoxvirus, PCPV and bovine papular stomatitis virus, BPSV). Here, we present the first genomic sequence of a reference strain of PCPV (VR634) along with the genomic sequence of a PPV (F00.120R) isolated in Finland from reindeer (Rangifer tarandus tarandus). The F00.120R and VR634 genomes are 135 and 145 kb in length and contain 131 and 134 putative genes, respectively, with their genome organization being similar to that of other PPVs. The predicted proteins of F00.120R and VR634 have an average amino acid sequence identity of over 95%, whereas they share only 88 and 73% amino acid identity with the ORFV and BPSV proteomes, respectively. The most notable differences were found near the genome termini. F00.120R lacks six and VR634 lacks three genes seen near the right terminus of other PPVs. Four genes at the left end of F00.120R and one in the middle of both genomes appear to be fragmented paralogues of other genes within the genome. VR634 has larger than expected inverted terminal repeats possibly as a result of genomic rearrangements. The high G+C content (64%) of these two viruses along with amino acid sequence comparisons and whole genome phylogenetic analyses confirm the classification of PCPV as a separate species within the genus Parapoxvirus and verify that the virus responsible for an outbreak of contagious stomatitis in reindeer over the winter of 1999-2000 can be classified as PCPV.
    Journal of General Virology 06/2010; 91(Pt 6):1560-76. · 3.53 Impact Factor
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    ABSTRACT: Orf virus (ORFV) is a zoonotic parapoxvirus that induces acute pustular skin lesions in sheep and humans. ORFV can reinfect its host and the discovery of several secreted immune modulatory factors that include a chemokine-binding protein (CBP) may explain this phenomenon. Dendritic cells (DC) are professional antigen presenting cells that induce adaptive immunity and their recruitment to sites of infection in skin and migration to peripheral lymph nodes is critically dependent on inflammatory and constitutive chemokine gradients respectively. Here we examined whether ORFV-CBP could disable these gradients using mouse models. Previously we established that ORFV-CBP bound murine inflammatory chemokines with high affinity and here we show that this binding spectrum extends to constitutive chemokines CCL19 and CCL21. Using cell-based chemotaxis assays, ORFV-CBP inhibited the movement of both immature and mature DC in response to these inflammatory and constitutive chemokines respectively. Moreover in C57BL/6 mice, intradermally injected CBP potently inhibited the recruitment of blood-derived DC to lipopolysaccharide-induced sites of skin inflammation and inhibited the migration of ex vivo CpG-activated DC to inguinal lymph nodes. Finally we showed that ORFV-CBP completely inhibited T responsiveness in the inguinal lymph nodes using intradermally injected DC pulsed with ovalbumin peptide and transfused transgenic T cells.
    Cellular Microbiology 05/2010; 12(5):665-76. · 4.82 Impact Factor
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    Min Mo, Stephen B Fleming, Andrew A Mercer
    Cell cycle (Georgetown, Tex.) 02/2010; 9(4):632-3. · 5.24 Impact Factor
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    Min Mo, Stephen B Fleming, Andrew A Mercer
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    ABSTRACT: The anaphase-promoting complex (APC), or cyclosome, is a ubiquitin ligase with major roles in cell cycle regulation. It is required for mitotic exit, but must be deactivated for the G(1)/S phase transition to occur. APC consists of at least 12 subunits with the catalytic core formed by a scaffold protein, APC2, and a RING-H2 protein, APC11. APC11 facilitates ubiquitin chain formation by recruiting ubiquitin-charged conjugating enzymes through its RING-H2 domain. We report that a small number of poxviruses encode RING-H2 proteins with sequence similarities to APC11. We show that a representative of these viral proteins mimics APC11 in its interactions with APC, but unlike APC11, the viral protein fails to promote ubiquitin chain formation. This absence of ubiquitin ligase activity is linked to a distinctive sequence variation within its RING-H2 domain. Expression of the viral protein led to cell cycle deregulation and the accumulation of APC substrates in a manner consistent with impaired APC function. Our data characterize this protein as a regulator of APC activity, and consequently, we have called it PACR (poxvirus APC/cyclosome regulator). Deletion of the PACR gene substantially reduced viral replication. Here, we report a viral mimic of an APC component and reveal an intriguing mechanism by which viruses can manipulate cell cycle progression and, thereby, promote their own replication.
    Proceedings of the National Academy of Sciences 11/2009; 106(46):19527-32. · 9.81 Impact Factor
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    ABSTRACT: We have previously shown that the Orf virus protein, ORFV125, is a potent inhibitor of the mitochondrial pathway of apoptosis and displays rudimentary sequence similarities to cellular anti-apoptotic Bcl-2 proteins. Here we investigate the proposal that ORFV125 acts in a Bcl-2-like manner to inhibit apoptosis. We show that the viral protein interacted with a range of BH3-only proteins (Bik, Puma, DP5, Noxa and all 3 isoforms of Bim) and neutralized their pro-apoptotic activity. In addition, ORFV125 bound to the active, but not the inactive, form of Bax, and reduced the formation of Bax dimers. Mutation of specific amino acids in ORFV125 that are conserved and functionally important in mammalian Bcl-2 family proteins led to loss of both binding and inhibitory functions. We conclude that ORFV125's mechanism of action is Bcl-2-like and propose that the viral protein's combined ability to bind to a range of BH3-only proteins as well as the active form of Bax provides significant protection against apoptosis. Furthermore, we demonstrate that the binding profile of ORFV125 is distinct to that of other poxviral Bcl-2-like proteins.
    Apoptosis 09/2009; 14(11):1317-30. · 3.61 Impact Factor

Publication Stats

2k Citations
322.79 Total Impact Points


  • 1989–2014
    • University of Otago
      • • Department of Microbiology and Immunology
      • • Virus Research Unit
      • • Department of Biochemistry
      Taieri, Otago Region, New Zealand
  • 2008
    • Gribbles Veterinary Pathology
      Hamilton, Victoria, Australia
  • 2004
    • The University of Western Ontario
      • Department of Microbiology and Immunology
      London, Ontario, Canada
  • 1998–2003
    • Moredun Research Institute
      • Department of Parasitology
      Penicuik, Scotland, United Kingdom
  • 1992
    • European Molecular Biology Laboratory
      Heidelburg, Baden-Württemberg, Germany
  • 1991
    • University of Reading
      Reading, England, United Kingdom
  • 1988
    • New Zealand Council for Educational Research
      Wellington, Wellington, New Zealand