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myxoma viral serpin, serp-1, inhibits human monocyte adhesion through regulation of actin-binding protein filamin b.serp-1 is a secreted myxoma viral serine protease inhibitor (serpin) with proven, highly effective, anti-inflammatory defensive activity during host cell infection, as well as potent immunomodulatory activity in a wide range of animal disease models. serp-1 binds urokinase-type plasminogen activator (upa) and the tissue-type pa, plasmin, and factor xa, requiring upa receptor (upar) for anti-inflammatory activity. to define serp-1-mediated effects on inflammatory cell activation, we examined the ...200919052145
myxoma virus selectively disrupts type i interferon signaling in primary human fibroblasts by blocking the activation of the janus kinase tyk2.poxviruses currently are known to disrupt jak-stat signal transduction induced by interferon (ifn) through two distinct mechanisms: (1) secreted poxviral ifn decoy receptors that prevent the initiation of ifn signaling from type i or ii receptors at the cell surface; and (2) poxviral phosphatase that dephosphorylates stat1 intracellularly. here, we report a novel mechanism by which poxviruses can inhibit jak-stat signaling in response to type i ifn. myxoma virus (mv) is a highly species-restrict ...200919254804
comparative analysis of poxvirus orthologues of the vaccinia virus e3 protein: modulation of protein kinase r activity, cytokine responses, and virus pathogenicity.poxviruses are important human and animal pathogens that have evolved elaborate strategies for antagonizing host innate and adaptive immunity. the e3 protein of vaccinia virus, the prototypic member of the orthopoxviruses, functions as an inhibitor of innate immune signaling and is essential for vaccinia virus replication in vivo and in many human cell culture systems. however, the function of orthologues of e3 expressed by poxviruses of other genera with different host specificity remains large ...201121917954
10 m-t7: measuring chemokine-modulating activity.chemokines are important for activation of a host of cellular immune and inflammatory responses including cell signaling, activation, and communication. m-t7, a myxoma virus protein, inhibits the activity of chemokines by direct binding to chemokines and/or with glycosaminoglycans (gags). to study the effects of this chemokine-modulating protein (cmp), we use a variety of in vitro and in vivo techniques to evaluate m-t7 inhibition of inflammatory cells. to quickly analyze the effects of m-t7, ch ...200919446727
myxoma virus m130r is a novel virulence factor required for lethal myxomatosis in rabbits.myxoma virus (mv) is a highly lethal, rabbit-specific poxvirus that induces a disease called myxomatosis in european rabbits. in an effort to understand the function of predicted immunomodulatory genes we have deleted various viral genes from mv and tested the ability of these knockout viruses to induce lethal myxomatosis. mv encodes a unique 15 kd cytoplasmic protein (m130r) that is expressed late (12h post infection) during infection. m130r is a non-essential gene for mv replication in rabbit, ...200919477207
oncolytic virotherapy for hematological malignancies.hematological malignancies such as leukemias, lymphomas, multiple myeloma (mm), and the myelodysplastic syndromes (mdss) primarily affect adults and are difficult to treat. for high-risk disease, hematopoietic stem cell transplant (hct) can be used. however, in the setting of autologous hct, relapse due to contamination of the autograft with cancer cells remains a major challenge. ex vivo manipulations of the autograft to purge cancer cells using chemotherapies and toxins have been attempted. be ...201122312362
genome sequence of sg33 strain and recombination between wild-type and vaccine myxoma viruses.myxomatosis in europe is the result of the release of a south america strain of myxoma virus in 1952. several attenuated strains with origins in south america or california have since been used as vaccines in the rabbit industry. we sequenced the genome of the sg33 myxoma virus vaccine strain and compared it with those of other myxoma virus strains. we show that sg33 genome carries a large deletion in its right end. furthermore, our data strongly suggest that the virus isolate from which sg33 is ...201121470452
myxoma virus and the leporipoxviruses: an evolutionary paradigm.myxoma virus (myxv) is the type species of the leporipoxviruses, a genus of chordopoxvirinae, double stranded dna viruses, whose members infect leporids and squirrels, inducing cutaneous fibromas from which virus is mechanically transmitted by biting arthropods. however, in the european rabbit (oryctolagus cuniculus), myxv causes the lethal disease myxomatosis. the release of myxv as a biological control for the wild european rabbit population in australia, initiated one of the great experiments ...201525757062
the α2,3-sialyltransferase encoded by myxoma virus is a virulence factor that contributes to immunosuppression.myxoma virus (myxv) induces a lethal disease called myxomatosis in european rabbits. myxv is one of the rare viruses that encodes an α2,3-sialyltransferase through its m138l gene. in this study, we showed that although the absence of the enzyme was not associated with any in vitro deficit, the m138l deficient strains are highly attenuated in vivo. indeed, while all rabbits infected with the parental and the revertant strains died within 9 days post-infection from severe myxomatosis, all but one ...201525705900
viral biocontrol: grand experiments in disease emergence and evolution.although viral emergence is commonly associated with cross-species transmission, the processes and determinants of viral evolution in a novel host environment are poorly understood. we address key questions in virus emergence and evolution using data generated from two unique natural experiments: the deliberate release of myxoma virus (myxv) and rabbit hemorrhagic disease virus (rhdv) as biological control (biocontrol) agents against the european rabbit in australia, and which have been of enorm ...201425455418
production of myxoma virus gateway entry and expression libraries and validation of viral protein expression.invitrogen's gateway technology is a recombination-based cloning method that allows for rapid transfer of numerous open reading frames (orfs) into multiple plasmid vectors, making it useful for diverse high-throughput applications. gateway technology has been utilized to create an orf library for myxoma virus (myxv), a member of the poxviridae family of dna viruses. myxv is the prototype virus for the genus leporipoxvirus, and is pathogenic only in european rabbits. myxv replicates exclusively i ...201121538302
a whole-genome rna interference screen for human cell factors affecting myxoma virus replication.myxoma virus (myxv) provides an important model for investigating host-pathogen interactions. recent studies have also highlighted how mutations in transformed human cells can expand the host range of this rabbit virus. although virus growth depends upon interactions between virus and host proteins, the nature of these interactions is poorly understood. to address this matter, we performed small interfering rna (sirna) screens for genes affecting myxv growth in human mda-mb-231 cells. by using s ...201323408614
myxoma virus combined with rapamycin treatment enhances adoptive t cell therapy for murine melanoma brain tumors.adoptive transfer of tumor-specific t cells has shown some success for treating metastatic melanoma. we evaluated a novel strategy to improve adoptive therapy by administering both t cells and oncolytic myxoma virus to mice with syngeneic b16.siy melanoma brain tumors. adoptive transfer of activated cd8(+) 2c t cells that recognize siy peptide doubled survival time, but siy-negative tumors recurred. myxoma virus killed b16.siy cells in vitro, and intratumoral injection of virus led to selective ...201121656158
field experimental vaccination campaigns against myxomatosis and their effectiveness in the wild.we conducted a field experiment in sw spain to test the efficacy of a myxomatosis vaccine, a viral disease strongly affecting wild rabbit populations, by assessing individual survival and antibody seroprevalence of monthly live-trapped, vaccinated (n=466) and unvaccinated (n=558) juvenile wild rabbits, between april and october 2007. eight percent of all juveniles caught from april to june showed maternal antibodies against myxomatosis, whereas all animals were seropositive to the disease after ...200919800438
infection of non-host species dendritic cells in vitro with an attenuated myxoma virus induces gene expression predicting efficacy as a vaccine vector.recombinant myxoma virus (myxv) can be produced without a loss of infectivity and their highly-specific host range makes them ideal candidates as vaccine vectors, although careful examination of their interactions with the immune system is necessary. similar to rabbit bone marrow-derived dendritic cells, ovine dendritic cells (dcs) can be infected by sg33, a myxv vaccine strain, and support recombinant antigen expression. the frequency of infected cells in the non-host was lower and the virus cy ...201121835800
myxoma virus induces type i ifn production in murine plasmacytoid dendritic cells via a tlr9/myd88, irf5/irf7, and ifnar-dependent pathway.poxviruses are large dna viruses that replicate in the cytoplasm of infected cells. myxoma virus is a rabbit poxvirus that belongs to the leporipoxvirus genus. it causes lethal disease called myxomatosis in european rabbits but cannot sustain any detectable infection in non-lagomorphs. vaccinia virus is a prototypal orthopoxvirus that was used as a vaccine to eradicate smallpox. myxoma virus is non-pathogenic in mice, whereas systemic infection with vaccinia can be lethal even in immunocompetent ...201121835795
exploring the antitumor effect of virus in malignant glioma.malignant gliomas are the most common type of primary malignant brain tumor with no effective treatments. current conventional therapies (surgical resection, radiation therapy, temozolomide (tmz), and bevacizumab administration) typically fail to eradicate the tumors resulting in the recurrence of treatment-resistant tumors. therefore, novel approaches are needed to improve therapeutic outcomes. oncolytic viruses (ovs) are excellent candidates as a more effective therapeutic strategy for aggress ...201726855472
viral serpin therapeutics from concept to clinic.over the past 19 years, we have developed a novel myxoma virus-derived anti-inflammatory serine protease inhibitor, termed a serpin, as a new class of immunomodulatory therapeutic. this review will describe the initial identification of viral serpins with anti-inflammatory potential, beginning with preclinical analysis of viral pathogenesis and proceeding to cell and molecular target analyses, and successful clinical trial. the central aim of this review is to describe the development of two ser ...201121683260
prevention of ebv lymphoma development by oncolytic myxoma virus in a murine xenograft model of post-transplant lymphoproliferative disease.epstein-barr virus (ebv) has been associated with a variety of epithelial and hematologic malignancies, including b-, t- and nk cell-lymphomas, hodgkin's disease (hd), post-transplant lymphoproliferative diseases (lpds), nasopharyngeal and gastric carcinomas, smooth muscle tumors, and hiv-associated lymphomas. currently, treatment options for ebv-associated malignancies are limited. we have previously shown that myxoma virus specifically targets various human solid tumors and leukemia cells in a ...201525843801
myxoma virus targets primary human leukemic stem and progenitor cells while sparing normal hematopoietic stem and progenitor cells. 200919865109
viral infections of rabbits.viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). however, clinicians seeing pet rabbits in north america infrequently encounter viral diseases although myxomatosis may be seen occasionally. the situation is different in europe and australia, where myxomatosis and rabbit hemorrhagic disease are endemic. advances in epidemiology and virol ...201323642871
infectious fibroma of rabbits : iii. the serial transmission of virus myxomatosum in cottontail rabbits, and cross-immunity tests with the fibroma virus.in the experiments presented, virus myxomatosum was observed to produce only a localized fibromatous or myxomatous orchitis when injected into the testicles of cottontail rabbits. this type of disease was quite unlike the acute fatal illness which the virus caused in domestic rabbits. 10 serial passages of virus myxomatosum through cottontail rabbits, covering a total elapsed time of 140 days, failed to alter its pathogenicity for domestic rabbits. although it proved impossible to convert the my ...193619870458
infectious myxomatosis of rabbits : preparation of elementary bodies and studies of serologically active materials associated with the disease.from the results of the experiments described in this paper it is obvious that large amounts of elementary bodies of myxoma can be obtained in a relatively pure state by means of the methods used. furthermore, it is evident that infectious myxomatosis is a viral disease in which elementary bodies of the same order of magnitude as vaccinal elementary bodies play a conspicuous rô1e in that they either represent the etiological agent or are intimately associated with it. the bodies are specifically ...193719870643
the superinfection of the rabbit papilloma (shope) by extraneous viruses.1. the potentialities that viruses have for the superinfection of virus tumors have not been recognized nor has the fact that a single cell can harbor more than one virus. 2. rabbit papillomas, induced by the papilloma virus (shope), were superinfected by b virus, myxoma virus, vaccinia virus, and probably, virus iii. similar attempts at superinfection by herpes virus were without success. the criteria for parasitization included the histopathological finding of specific inclusion bodies, the re ...194719871661
molecular and serological analysis of the epidemiology of myxoma virus in rabbits.the epidemiology of myxoma virus was studied by serology and molecular analysis of restriction fragment length polymorphisms (rflps) in genomic dna. 159 isolates of myxoma virus were made over a period of 5 spring/summer epidemics from 12 field sites in south-eastern australia. virus isolates were classified into 10 genetic types using rflps detected with a panel of nine restriction endonucleases. between 3 and 6 different genetic types were found during spring/summer periods across all sites an ...201020018465
myxoma virus virotherapy for glioma in immunocompetent animal models: optimizing administration routes and synergy with rapamycin.oncolytic myxoma virus (myxv) is being developed as a novel virotherapeutic against human brain cancer and has promising activity against human brain tumor models in immunocompromised hosts. because an intact immune system could reduce its efficacy, the purpose of this study was to evaluate the oncolytic potential of myxv in immunocompetent racine glioma models. here, we report that myxv infects and kills all racine cell glioma lines and that its effects are enhanced by rapamycin. intratumoral a ...201020068158
pharmacological manipulation of the akt signaling pathway regulates myxoma virus replication and tropism in human cancer cells.viruses have evolved an assortment of mechanisms for regulating the akt signaling pathway to establish a cellular environment more favorable for viral replication. myxoma virus (myxv) is a rabbit-specific poxvirus that encodes many immunomodulatory factors, including an ankyrin repeat-containing host range protein termed m-t5 that functions to regulate tropism of myxv for rabbit lymphocytes and certain human cancer cells. myxv permissiveness in these human cancer cells is dependent upon the dire ...201020106927
mnf, an ankyrin repeat protein of myxoma virus, is part of a native cellular scf complex during viral infection.myxoma virus (myxv), a member of the poxviridae family, is the agent responsible for myxomatosis, a fatal disease in the european rabbit (oryctolagus cuniculus). like all poxviruses, myxv is known for encoding multiple proteins that regulate cellular signaling pathways. among them, four proteins share the same ank/pranc structure: m148r, m149r, mnf (myxoma nuclear factor) and m-t5, all of them described as virulence factors. this family of poxvirus proteins, recently identified, has drawn consid ...201020211013
the viral tropism of two distinct oncolytic viruses, reovirus and myxoma virus, is modulated by cellular tumor suppressor gene status.replication-competent oncolytic viruses hold great potential for the clinical treatment of many cancers. importantly, many oncolytic virus candidates, such as reovirus and myxoma virus, preferentially infect cancer cells bearing abnormal cellular signaling pathways. reovirus and myxoma virus are highly responsive to activated ras and akt signaling pathways, respectively, for their specificity for viral oncolysis. however, considering the complexity of cancer cell populations, it is possible that ...201020473328
myxoma virus therapy for human embryonal rhabdomyosarcoma in a nude mouse model.rhabdomyosarcoma (rms) is a devastating tumor of young people that is difficult to cure. to determine if oncolytic virus therapy can improve outcomes in individuals with rms, myxoma virus expressing a red fluorescent protein (myxv-red) was evaluated for antitumoral effects using a murine model of rms. fluorescent protein was expressed in four rms cell lines inoculated with myxv-red, indicating that these cells were semipermissive to myxv infection. myxv-red replication and cytopathic effects wer ...201627579297
benign rabbit caliciviruses exhibit evolutionary dynamics similar to those of their virulent relatives.two closely related caliciviruses cocirculate in australia: rabbit hemorrhagic disease virus (rhdv) and rabbit calicivirus australia 1 (rcv-a1). rcv-a1 causes benign enteric infections in the european rabbit (oryctolagus cuniculus) in australia and new zealand, while its close relative rhdv causes a highly pathogenic infection of the liver in the same host. the comparison of these viruses provides important information on the nature and trajectory of virulence evolution, particularly as highly v ...201627512059
molecular characterization of sg33 and borghi vaccines used against myxomatosis.myxoma virus is a poxvirus responsible for myxomatosis in european rabbits (oryctolagus cuniculus). the entire genome of the myxoma virus has been sequenced, allowing a systemic survey of the functions of a large number of putative pathogenic factors that this virus expresses to subvert the immune and inflammatory pathways of infected rabbit hosts. in italy, industrial rabbits are mostly vaccinated against myxomatosis using the attenuated myxoma virus strains borghi or sg33. we have identified g ...201020598407
the immunoregulatory properties of oncolytic myxoma virus and their implications in therapeutics.myxoma virus (myxv) is a poxvirus with a strict rabbit-specific host-tropism for pathogenesis. the immunoregulatory factors encoded by myxv can suppress some functions of immune effectors from other species. we review their mechanisms of action, implications in therapeutics and the potential to improve myxv as an oncolytic agent in humans.201020832500
cloning and characterization of a viral α2-3-sialyltransferase (vst3gal-i) for the synthesis of sialyl lewisx.sialyl lewis(x) (sle(x), siaα2-3galβ1-4(fucα1-3)glcnacβor) is an important sialic acid-containing carbohydrate epitope involved in many biological processes such as inflammation and cancer metastasis. in the biosynthetic process of sle(x), α2-3-sialyltransferase-catalyzed sialylation generally proceeds prior to α1-3-fucosyltransferase-catalyzed fucosylation. for the chemoenzymatic synthesis of sle(x) containing different sialic acid forms, however, it would be more efficient if diverse sialic ac ...201020978012
a randomized controlled, phase 2 trial of the viral serpin serp-1 in patients with acute coronary syndromes undergoing percutaneous coronary intervention.vascular inflammation can lead to plaque instability and acute coronary syndromes (acs). viruses produce potent immunomodulating proteins that regulate key inflammatory pathways. a myxoma virus-derived serpin serp-1 reduces inflammatory cell invasion and plaque growth in vascular injury models. our objective was to evaluate the safety and efficacy of serp-1 in patients with acs undergoing percutaneous coronary intervention.201021062996
myxoma virus induces apoptosis in cultured feline carcinoma cells.there is growing interest in utilizing replicating oncolytic viruses as cancer therapeutics agents. the effectiveness of myxoma virus-induced oncolysis was evaluated in two feline cancer cell cultures. although myxoma virus is a rabbit-specific pathogen, protein expression driven by myxoma virus and production of infectious viral particles were detected. cell death occurred in primary feline cancer cells within 48h of inoculation with myxoma virus. future studies to determine if other feline neo ...201122100245
biological effects of a de novo designed myxoma virus peptide analogue: evaluation of cytotoxicity on tumor cells.the resonant recognition model (rrm) is a physico-mathematical model that interprets protein sequence linear information using digital signal processing methods. in this study the rrm concept was employed for structure-function analysis of myxoma virus (mv) proteins and the design of a short bioactive therapeutic peptide with mv-like antitumor/cytotoxic activity.201121949758
structural basis for antagonizing a host restriction factor by c7 family of poxvirus host-range proteins.human sterile alpha motif domain-containing 9 (samd9) protein is a host restriction factor for poxviruses, but it can be overcome by some poxvirus host-range proteins that share homology with vaccinia virus c7 protein. to understand the mechanism of action for this important family of host-range factors, we determined the crystal structures of c7 and myxoma virus m64, a c7 family member that is unable to antagonize samd9. despite their different functions and only 23% sequence identity, the two ...201526578811
molecular species identification, host preference and detection of myxoma virus in the anopheles maculipennis complex (diptera: culicidae) in southern england, uk.determining the host feeding patterns of mosquitoes by identifying the origin of their blood-meals is an important part of understanding the role of vector species in current and future disease transmission cycles. collecting large numbers of blood-fed mosquitoes from the field is difficult, therefore it is important to maximise the information obtained from each specimen. this study aimed to use mosquito genome sequence to identify the species within anopheles maculipennis sensu lato (an. macul ...201526271277
biological characterization and next-generation genome sequencing of the unclassified cotia virus span232 (poxviridae).cotia virus (cotv) span232 was isolated in 1961 from sentinel mice at cotia field station, são paulo, brazil. attempts to classify cotv within a recognized genus of the poxviridae have generated contradictory findings. studies by different researchers suggested some similarity to myxoma virus and swinepox virus, whereas another investigation characterized cotv span232 as a vaccinia virus strain. because of the lack of consensus, we have conducted an independent biological and molecular character ...201222345477
myxoma virus m156 is a specific inhibitor of rabbit pkr but contains a loss-of-function mutation in australian virus isolates.myxoma virus (myxv) is a rabbit-specific poxvirus, which is highly virulent in european rabbits. the attenuation of myxv and the increased resistance of rabbits following the release of myxv in australia is one of the best-documented examples of host-pathogen coevolution. to elucidate the molecular mechanisms that contribute to the restriction of myxv infection to rabbits and myxv attenuation in the field, we have studied the interaction of the myxv protein m156 with the host antiviral protein k ...201626903626
myxoma virus-mediated oncolysis of ascites-derived human ovarian cancer cells and spheroids is impacted by differential akt activity.we propose that metastatic epithelial ovarian cancer (eoc) is a potential therapeutic target for the oncolytic agent, myxoma virus (myxv).201222306204
the ex vivo purge of cancer cells using oncolytic viruses: recent advances and clinical implications.hematological malignancies are treated with intensive high-dose chemotherapy, with or without radiation. this is followed by hematopoietic stem cell (hsc) transplantation (hsct) to rescue or reconstitute hematopoiesis damaged by the anticancer therapy. autologous hsc grafts may contain cancer cells and purging could further improve treatment outcomes. similarly, allogeneic hsct may be improved by selectively purging alloreactive effector cells from the graft rather than wholesale immune cell dep ...201527512666
pseudogenization of the mcp-2/ccl8 chemokine gene in european rabbit (genus oryctolagus), but not in species of cottontail rabbit (sylvilagus) and hare (lepus).recent studies in human have highlighted the importance of the monocyte chemotactic proteins (mcp) in leukocyte trafficking and their effects in inflammatory processes, tumor progression, and hiv-1 infection. in european rabbit (oryctolagus cuniculus) one of the prime mcp targets, the chemokine receptor ccr5 underwent a unique structural alteration. until now, no homologue of mcp-2/ccl8a, mcp-3/ccl7 or mcp-4/ccl13 genes have been reported for this species. this is interesting, because at least t ...201222894773
myxoma virus dsrna binding protein m029  inhibits the type i ifn-induced antiviral state in a  highly species-specific fashion.myxoma virus (myxv) is leporipoxvirus that possesses a specific rabbit-restricted host tropism but exhibits a much broader  cellular host range in cultured cells. myxv is able to efficiently  block all aspects of the type i interferon (ifn)-induced  antiviral  state  in rabbit cells, partially in  human  cells  and  very  poorly  in  mouse  cells.  the mechanism(s) of this species-specific inhibition of  type i ifn-induced antiviral state is not well understood. here we demonstrate that myxv enc ...201728157174
systemic therapy with oncolytic myxoma virus cures established residual multiple myeloma in mice.multiple myeloma is an incurable malignancy of plasma b-cells. traditional chemotherapeutic regimes often induce initial tumor regression; however, virtually all patients eventually succumb to relapse caused by either reintroduction of disease during autologous transplant or expansion of chemotherapy resistant minimal residual disease. it has been previously demonstrated that an oncolytic virus known as myxoma can completely prevent myeloma relapse caused by reintroduction of malignant cells dur ...201627933316
genetic variability of myxoma virus genomes.myxomatosis is a recurrent problem on rabbit farms throughout europe despite the success of vaccines. to identify gene variations of field and vaccine strains that may be responsible for changes in virulence, immunomodulation, and immunoprotection, the genomes of 6 myxoma virus (myxv) strains were sequenced: german field isolates munich-1, fli-h, 2604, and 3207; vaccine strain mav; and challenge strain za. the analyzed genomes ranged from 147.6 kb (strain mav) to 161.8 kb (strain 3207). all sequ ...201727903800
effects of myxoma virus and rabbit hemorrhagic disease virus on the physiological condition of wild european rabbits: is blood biochemistry a useful monitoring tool?myxomatosis and rabbit hemorrhagic disease (rhd) are the major viral diseases that affect the wild european rabbit (oryctolagus cuniculus). these diseases arrived in europe within the last decades and have caused wild rabbit populations to decline dramatically. both viruses are currently considered to be endemic in the iberian peninsula; periodic outbreaks that strongly impact wild populations regularly occur. myxoma virus (mv) and rabbit hemorrhagic disease virus (rhdv) alter the physiology of ...201627892861
myxoma virus lacking the pyrin-like protein m013 is sensed in human myeloid cells by both nlrp3 and multiple toll-like receptors, which independently activate the inflammasome and nf-κb innate response pathways.the myxoma virus (myxv)-encoded pyrin domain-containing protein m013 coregulates inflammatory responses mediated by both the inflammasome and the nf-κb pathways. infection of human thp-1 monocytic cells with a myxv construct deleted for the m013 gene (vmyxm013-ko), but not the parental myxv, activates both the inflammasome and nf-κb pathways and induces a spectrum of proinflammatory cytokines and chemokines, like interleukin-1β (il-1β), tumor necrosis factor (tnf), il-6, and monocyte chemoattrac ...201121957307
myxoma virus sensitizes cancer cells to gemcitabine and is an effective oncolytic virotherapeutic in models of disseminated pancreatic cancer.myxoma virus (myxv) is a novel oncolytic virus that has been shown to replicate in pancreatic cancer cells, but its efficacy in animal models of pancreatic cancer has not been determined. the efficacy of myxv as monotherapy or in combination with gemcitabine was evaluated in intraperitoneal dissemination (ipd) models of pancreatic cancer. the effects of an intact immune system on the efficacy of myxv therapy was tested by comparing immunodeficient versus immunocompetent murine models and combina ...201222233582
a survey of host range genes in poxvirus genomes.poxviruses are widespread pathogens, which display extremely different host ranges. whereas some poxviruses, including variola virus, display narrow host ranges, others such as cowpox viruses naturally infect a wide range of mammals. the molecular basis for differences in host range are poorly understood but apparently depend on the successful manipulation of the host antiviral response. some poxvirus genes have been shown to confer host tropism in experimental settings and are thus called host ...201223268114
rabbit cd200r binds host cd200 but not cd200-like proteins from poxviruses.cd200 is a widely distributed membrane protein that gives inhibitory signals through its receptor (cd200r) on myeloid cells. cd200 has been acquired by herpesviruses where it has been shown to interact with host cd200r and downmodulate the immune system. it has been hypothesized that poxviruses have acquired cd200; but the potential orthologues show less similarity to their hosts. myxoma virus m141 protein is a potential cd200 orthologue with a potent immune modulatory function in rabbits. here, ...201626590792
genetic characterization of interleukins (il-1α, il-1β, il-2, il-4, il-8, il-10, il-12a, il-12b, il-15 and il-18) with relevant biological roles in lagomorphs.ils, as essential innate immune modulators, are involved in an array of biological processes. in the european rabbit (oryctolagus cuniculus) il-1α, il-1β, il-2, il-4, il-8, il-10, il-12a, il-12b, il-15 and il-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. in this study we characterized these ils in six lagomorpha species (european rabbit, pygmy rabbit, two cottontail rabbit species, european brown ...201526395994
targeting b16 tumors in vivo with peptide-conjugated gold nanoparticles.this study examines the effects of polyethylene glycol (peg) and peptide conjugation on the biodistribution of ultrasmall (2.7 nm) gold nanoparticles in mice bearing b16 melanoma allografts. nanoparticles were delivered intravenously, and biodistribution was measured at specific timepoints by organ digestion and inductively coupled plasma mass spectrometry. all major organs were examined. two peptides were tested: the cyclic rgd peptide (crgd, which targets integrins); and a recently described p ...201526111959
vaccine breaks: outbreaks of myxomatosis on spanish commercial rabbit farms.despite the success of vaccination against myxoma virus, myxomatosis remains a problem on rabbit farms throughout spain and europe. in this study we set out to evaluate possible causes of myxoma virus (myxv) vaccine failures addressing key issues with regard to pathogen, vaccine and vaccination strategies. this was done by genetically characterising myxv field isolates from farm outbreaks, selecting a representative strain for which to assay its virulence and measuring the protective capability ...201526009303
targeting gallbladder cancer: hyaluronan sensitizes cancer cells to chemo-therapeutics.gallbladder cancer is the most common biliary tract malignancy and the fifth most common gastrointestinal malignancy. chemo-resistance is the most remarkable characteristic of gallbladder cancer. the relatively dense extracellular space in tumor is the main barrier to nanotherapeutics' anticancer efficacy. hyaluronan (ha) was shown in our previous study to significantly improve the myxoma virus distribution via promoting the mmp-9 production, which degrades collagen iv. we demonstrated that ha i ...201525973074
myxoma virus suppresses proliferation of activated t lymphocytes yet permits oncolytic virus transfer to cancer cells.allogeneic hematopoietic cell transplant (allo-hct) can be curative for certain hematologic malignancies, but the risk of graft-versus-host disease (gvhd) is a major limitation for wider application. ideally, strategies to improve allo-hct would involve suppression of t lymphocytes that drive gvhd while sparing those that mediate graft-versus-malignancy (gvm). recently, using a xenograft model, we serendipitously discovered that myxoma virus (myxv) prevented gvhd while permitting gvm. in this st ...201525904246
oncolytic poxviruses.current standard treatments of cancer can prolong survival of many cancer patients but usually do not effectively cure the disease. oncolytic virotherapy is an emerging therapeutic for the treatment of cancer that exploits replication-competent viruses to selectively infect and destroy cancerous cells while sparing normal cells and tissues. clinical and/or preclinical studies on oncolytic viruses have revealed that the candidate viruses being tested in trials are remarkably safe and offer potent ...201425839047
ex vivo oncolytic virotherapy with myxoma virus arms multiple allogeneic bone marrow transplant leukocytes to enhance graft versus tumor.allogeneic stem cell transplant-derived t cells have the potential to seek and eliminate sites of residual cancer that escaped primary therapy. oncolytic myxoma virus (myxv) exhibits potent anti-cancer efficacy against human cancers like multiple myeloma (mm) and can arm transplant-derived t cells to become more effective cancer killers in vitro and in an immunodeficient xenotransplant murine model. here, we tested ex vivo myxv virotherapy against residual murine mm in immunocompetent mice using ...201728345022
tumor localized secretion of soluble pd1 enhances oncolytic virotherapy.oncolytic virotherapy represents an attractive option for the treatment of a variety of aggressive or refractory tumors. while this therapy is effective at rapidly debulking directly injected tumor masses, achieving complete eradication of established disease has proven difficult. one method to overcome this challenge is to use oncolytic viruses to induce secondary anti-tumor immune responses. unfortunately, while the initial induction of these immune responses is typically robust, their subsequ ...201728314785
genomic and phenotypic characterization of myxoma virus from great britain reveals multiple evolutionary pathways distinct from those in australia.the co-evolution of myxoma virus (myxv) and the european rabbit occurred independently in australia and europe from different progenitor viruses. although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of myxv evolution in europe mirror those observed in australia is unknown. we addressed this question using viruses isolated in the united kingdom early in the myxv epizootic (1954-1955) and between 2008-2013. the later uk viruses fell into t ...201728253375
an interaction domain in human samd9 is essential for myxoma virus host-range determinant m062 antagonism of host anti-viral function.in humans, deleterious mutations in the sterile α motif domain protein 9 (samd9) gene are associated with cancer, inflammation, weakening of the immune response, and developmental arrest. however, the biological function of samd9 and its sequence-structure relationships remain to be characterized. previously, we found that an essential host range factor, m062 protein from myxoma virus (myxv), antagonized the function of human samd9. in this study, we examine the interaction between m062 and huma ...201728157624
an invasive non-native mammal population conserves genetic diversity lost from its native range.invasive, non-native species are one of the major causes of global biodiversity loss. although they are, by definition, successful in their non-native range, their populations generally show major reductions in their genetic diversity during the demographic bottleneck they experience during colonization. by investigating the mitochondrial genetic diversity of an invasive non-native species, the stoat mustela erminea, in new zealand and comparing it to diversity in the species' native range in gr ...201525655531
in vitro screen of a small molecule inhibitor drug library identifies multiple compounds that synergize with oncolytic myxoma virus against human brain tumor-initiating cells.brain tumor-initiating cells (btics) are stem-like cells hypothesized to form a disease reservoir that mediates tumor recurrence in high-grade gliomas. oncolytic virotherapy uses replication-competent viruses to target and kill malignant cells and has been evaluated in clinic for glioma therapy with limited results. myxoma virus (myxv) is a safe and highly effective oncolytic virus (ov) in conventional glioma models but, as seen with other ovs, is only modestly effective for patient-derived btic ...201525605818
stress beyond translation: poxviruses and more.poxviruses are large double-stranded dna viruses that form viral factories in the cytoplasm of host cells. these viruses encode their own transcription machinery, but rely on host translation for protein synthesis. thus, poxviruses have to cope with and, in most cases, reprogram host translation regulation. granule structures, called antiviral granules (avgs), have been observed surrounding poxvirus viral factories. avg formation is associated with abortive poxvirus infection, and avgs contain p ...201627314378
evolutionary clash between myxoma virus and rabbit pkr in australia. 201627035991
therapeutics for graft-versus-host disease: from conventional therapies to novel virotherapeutic strategies.allogeneic hematopoietic stem cell transplantation (allo-hsct) has a curative potential for many hematologic malignancies and blood diseases. however, the success of allo-hsct is limited by graft-versus-host disease (gvhd), an immunological syndrome that involves inflammation and tissue damage mediated by donor lymphocytes. despite immune suppression, gvhd is highly incident even after allo-hsct using human leukocyte antigen (hla)-matched donors. therefore, alternative and more effective therapi ...201627011200
m011l-deficient oncolytic myxoma virus induces apoptosis in brain tumor-initiating cells and enhances survival in a novel immunocompetent mouse model of glioblastoma.myxoma virus (myxv) is a promising oncolytic agent and is highly effective against immortalized glioma cells but less effective against brain tumor initiating cells (btics), which are believed to mediate glioma development/recurrence. myxv encodes various proteins to attenuate host cell apoptosis, including an antiapoptotic bcl-2 homologue known as m011l. such proteins may limit the ability of myxv to kill btics, which have heightened resistance to apoptosis. we hypothesized that infecting btics ...201626962017
ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells.relapsing disease is a major challenge after hematopoietic cell transplantation for hematological malignancies. myxoma virus (myxv) is an oncolytic virus that can target and eliminate contaminating cancer cells from auto-transplant grafts. the aims of this study were to examine the impact of myxv on normal hematopoietic stem and progenitor cells and define the optimal treatment conditions for ex vivo virotherapy.201626857235
myxoma virus induces ligand independent extrinsic apoptosis in human myeloma cells.multiple myeloma is a clonal malignancy of plasma b cells. although recent advances have improved overall prognosis, virtually all myeloma patients still succumb to relapsing disease. therefore, novel therapies to treat this disease remain urgently needed. we have recently shown that treatment of human multiple myeloma cells with an oncolytic virus known as myxoma results in rapid cell death even in the absence of viral replication; however, the specific mechanisms and pathways involved remain u ...201626803534
myxomatosis.myxomatosis, a major disease of european rabbits (oryctolagus cuniculus), is enzootic on several continents. the disease is infectious, virulent and contagious. the pathogen is a virus of the family poxviridae, genus leporipoxvirus. in its classic form the disease is often fatal, characterised by severe immunosuppression and the appearance of skin pseudotumours (myxomas); it is conducive to effective mechanical transmission by many biting arthropods. atypical clinical forms, referred to as amyxo ...201526601455
myxoma virus expressing a fusion protein of interleukin-15 (il15) and il15 receptor alpha has enhanced antitumor activity.myxoma virus, a rabbit poxvirus, can efficiently infect various types of mouse and human cancer cells. it is a strict rabbit-specific pathogen, and is thought to be safe as a therapeutic agent in all non-rabbit hosts tested including mice and humans. interleukin-15 (il15) is an immuno-modulatory cytokine with significant potential for stimulating anti-tumor t lymphocytes and nk cells. co-expression of il15 with the α subunit of il15 receptor (il15rα) greatly enhances il15 stability and bioavaila ...201425329832
cutaneous lesions in pet rabbits following subcutaneous administration of a novel bivalent vaccine against myxomatosis and rabbit haemorrhagic disease.a novel bivalent vaccine to protect against myxomatosis and rabbit haemorrhagic disease is commercially available for pet rabbits.201425227274
increased virulence of rabbit haemorrhagic disease virus associated with genetic resistance in wild australian rabbits (oryctolagus cuniculus).the release of myxoma virus (myxv) and rabbit haemorrhagic disease virus (rhdv) in australia with the aim of controlling overabundant rabbits has provided a unique opportunity to study the initial spread and establishment of emerging pathogens, as well as their co-evolution with their mammalian hosts. in contrast to myxv, which attenuated shortly after its introduction, rapid attenuation of rhdv has not been observed. by studying the change in virulence of recent field isolates at a single field ...201425146599
recombinant myxoma virus lacking all poxvirus ankyrin-repeat proteins stimulates multiple cellular anti-viral pathways and exhibits a severe decrease in virulence.although the production of single gene knockout viruses is a useful strategy to study viral gene functions, the redundancy of many host interactive genes within a complex viral genome can obscure their collective functions. in this study, a rabbit-specific poxvirus, myxoma virus (myxv), was genetically altered to disrupt multiple members of the poxviral ankyrin-repeat (ank-r) protein superfamily, m-t5, m148, m149 and m150. a particularly robust activation of the nf-κb pathway was observed in a54 ...201425068401
the control of anaplastic thyroid carcinoma cell lines by oncolytic poxviruses.anaplastic thyroid cancer (atc) is rare, but its clinical presentation is often dramatic and aggressive and is nearly uniformly fatal. oncolytic viral therapy is a potential strategy to improve outcomes for patients suffering with this disease.201425038405
targeting gallbladder carcinoma: bone marrow-derived stem cells as therapeutic delivery vehicles of myxoma virus.gallbladder carcinoma (gbc) has a high mortality rate, requiring synergistic anti-tumor management for effective treatment. the myxoma virus (myxv) exhibits a modest clinical value through its oncolytic potential and narrow host tropism.201424931255
suppression of collagen-induced arthritis with a serine proteinase inhibitor (serpin) derived from myxoma virus.many viruses encode virulence factors to facilitate their own survival by modulating a host's inflammatory response. one of these factors, secreted from cells infected with myxoma virus, is the serine proteinase inhibitor (serpin) serp-1. because serp-1 had demonstrated anti-inflammatory properties in arterial injury models and viral infections, it was cloned and evaluated for therapeutic efficacy in collagen-induced arthritis (cia). clinical severity was significantly lower in the serp-1 protoc ...201424845791
targeting gallbladder cancer: oncolytic virotherapy with myxoma virus is enhanced by rapamycin in vitro and further improved by hyaluronan in vivo.gallbladder carcinoma (gbc) is highly lethal, and effective treatment will require synergistic anti-tumor management. the study is aimed at investigating the oncolytic value of myxoma virus (myxv) infection against gbc and optimizing myxv oncolytic efficiency.201424725816
multi-event capture-recapture modeling of host-pathogen dynamics among european rabbit populations exposed to myxoma and rabbit hemorrhagic disease viruses: common and heterogeneous patterns.host-pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. we applied a multi-event capture-recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and rabbit hemorrhagic disease virus (mv and rhdv). although the populations shared the same climatic and management conditions, mv and rhdv dynam ...201424708296
early infections by myxoma virus of young rabbits (oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations.the role of maternal antibodies is to protect newborns against acute early infection by pathogens. this can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. we carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the di ...201424589193
myxoma virus attenuates expression of activating transcription factor 4 (atf4) which has implications for the treatment of proteasome inhibitor-resistant multiple myeloma.the recent development of chemotherapeutic proteasome inhibitors, such as bortezomib, has improved the outcomes of patients suffering from the plasma cell malignancy multiple myeloma. unfortunately, many patients treated with these drugs still suffer relapsing disease due to treatment-induced upregulation of the antiapoptotic protein mcl1. we have recently demonstrated that an oncolytic poxvirus, known as myxoma, can rapidly eliminate primary myeloma cells by inducing cellular apoptosis. the eff ...201527512665
evidence for differential viral oncolytic efficacy in an in vitro model of epithelial ovarian cancer metastasis.epithelial ovarian cancer is unique among most carcinomas in that metastasis occurs by direct dissemination of malignant cells traversing throughout the intraperitoneal fluid. accordingly, we test new therapeutic strategies using an in vitro three-dimensional spheroid suspension culture model that mimics key steps of this metastatic process. in the present study, we sought to uncover the differential oncolytic efficacy among three different viruses-myxoma virus, double-deleted vaccinia virus, an ...201527119108
samd9 is an innate antiviral host factor with stress response properties that can be antagonized by poxviruses.we show that samd9 is an innate host antiviral stress response element that participates in the formation of antiviral granules. poxviruses, myxoma virus and vaccinia virus specifically, utilize a virus-encoded host range factor(s), such as a member of the c7l superfamily, to antagonize samd9 to prevent granule formation in a eukaryotic initiation factor 2α (eif2α)-independent manner. when samd9 is stimulated due to failure of the viral antagonism during infection, the resulting antiviral granul ...201525428864
gene delivery of a viral anti-inflammatory protein to combat ocular inflammation.inflammation of the retina is a contributing factor in ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration (amd). the m013 immunomodulatory protein from myxoma virus has been shown to interfere with the proinflammatory signaling pathways involving both the nlrp3 inflammasome and nf-κb. we have developed and characterized an adeno-associated viral (aav) vector that delivers a secretable and cell-penetrating form of the m013 protein (tatm013). the expressed ...201525420215
cellular factors promoting resistance to effective treatment of glioma with oncolytic myxoma virus.oncolytic virus therapy is being evaluated in clinical trials for human glioma. while it is widely assumed that the immune response of the patient to the virus infection limits the utility of the therapy, investigations into the specific cell type(s) involved in this response have been performed using nonspecific pharmacologic inhibitors or allogeneic models with compromised immunity. to identify the immune cells that participate in clearing an oncolytic infection in glioma, we used flow cytomet ...201425336188
myxoma virus oncolytic efficiency can be enhanced through chemical or genetic disruption of the actin cytoskeleton.myxoma virus (myxv) is one of many animal viruses that exhibit oncolytic properties in transformed human cells. compared to orthopoxviruses like vaccinia (vacv), myxv spreads inefficiently, which could compromise its use in treating tumors and their associated metastases. the vacv f11 protein promotes virus exit and rapid spread by inhibiting rho signalling, which results in a disruption of cortical actin. we have previously shown that although myxv lacks an f11 homolog, the f11l gene can be int ...201324391902
development and validation of a real time pcr for the detection of myxoma virus based on the diploid gene m000.5l/r.the myxoma virus (myxv) causes severe infections in european rabbits that may reach mortality rates up to 100% depending on the viral strain. the typical symptoms and lesions induced by the virus are usually enough to permit the correct clinical diagnosis. however, in peracute forms the infection may be accompanied by unspecific symptoms. sudden death may also occur without evident clinical signs of myxomatosis. likewise, a clinical diagnosis of atypical forms of myxomatosis (amyxomatous) is oft ...201424300832
myxoma virus infection promotes nk lysis of malignant gliomas in vitro and in vivo.myxoma virus (myxv) is a well-established oncolytic agent against different types of tumors. myxv is also known for its immunomodulatory properties in down-regulating major histocompatibility complex (mhc) i surface expression (via the m153r gene product, a viral e3-ubiquitin ligase) and suppressing t cell killing of infected target cells. mhc i down-regulation, however, favors nk cell activation. brain tumors including gliomas are characterized by high mhc i expression with impaired nk activity ...201323762498
resistance to oncolytic myxoma virus therapy in nf1(-/-)/trp53(-/-) syngeneic mouse glioma models is independent of anti-viral type-i interferon.despite promising preclinical studies, oncolytic viral therapy for malignant gliomas has resulted in variable, but underwhelming results in clinical evaluations. of concern are the low levels of tumour infection and viral replication within the tumour. this discrepancy between the laboratory and the clinic could result from the disparity of xenograft versus syngeneic models in determining in vivo viral infection, replication and treatment efficacy. here we describe a panel of primary mouse gliom ...201323762429
treating brain tumor-initiating cells using a combination of myxoma virus and rapamycin.intratumoral heterogeneity in glioblastoma multiforme (gbm) poses a significant barrier to therapy in certain subpopulation such as the tumor-initiating cell population, being shown to be refractory to conventional therapies. oncolytic virotherapy has the potential to target multiple compartments within the tumor and thus circumvent some of the barriers facing conventional therapies. in this study, we investigate the oncolytic potential of myxoma virus (myxv) alone and in combination with rapamy ...201323585629
evolution of viral sensing rig-i-like receptor genes in leporidae genera oryctolagus, sylvilagus, and lepus.one of the most severe european rabbit (oryctolagus cuniculus) pathogens is myxoma virus (myxv), a rabbit-specific leporipoxvirus that causes the highly lethal disease myxomatosis. other leporid genera, sylvilagus and lepus, encompass species with variable susceptibilities to myxv, but these do not develop the lethal form of the disease. the protective role of the retinoic acid-inducible gene-i (rig-i/ddx58) in sensing myxv in nonpermissive human myeloid cells prompted the study of the rig-i-lik ...201424220721
genome scale evolution of myxoma virus reveals host-pathogen adaptation and rapid geographic spread.the evolutionary interplay between myxoma virus (myxv) and the european rabbit (oryctolagus cuniculus) following release of the virus in australia in 1950 as a biological control is a classic example of host-pathogen coevolution. we present a detailed genomic and phylogeographic analysis of 30 strains of myxv, including the australian progenitor strain standard laboratory strain (sls), 24 australian viruses isolated from 1951 to 1999, and three isolates from the early radiation in britain from 1 ...201324067966
viral skin diseases of the rabbit.this article describes the viral skin diseases affecting the domestic rabbit, the most important being myxomatosis. transmission and pathogenesis, clinical signs, diagnosis, treatment, and control are described and the article will be of interest to veterinary practitioners who treat rabbits. shope fibroma virus, shope papilloma virus, and rabbitpox are also discussed.201324018033
comparative analysis of the complete genome sequence of the california msw strain of myxoma virus reveals potential host adaptations.myxomatosis is a rapidly lethal disease of european rabbits that is caused by myxoma virus (myxv). the introduction of a south american strain of myxv into the european rabbit population of australia is the classic case of host-pathogen coevolution following cross-species transmission. the most virulent strains of myxv for european rabbits are the californian viruses, found in the pacific states of the united states and the baja peninsula, mexico. the natural host of californian myxv is the brus ...201323986601
myxoma virus protein m029 is a dual function immunomodulator that inhibits pkr and also conscripts rha/dhx9 to promote expanded host tropism and viral replication.myxoma virus (myxv)-encoded protein m029 is a member of the poxvirus e3 family of dsrna-binding proteins that antagonize the cellular interferon signaling pathways. in order to investigate additional functions of m029, we have constructed a series of targeted m029-minus (vmyx-m029ko and vmyx-m029id) and v5-tagged m029 myxv. we found that m029 plays a pivotal role in determining the cellular tropism of myxv in all mammalian cells tested. the m029-minus viruses were able to replicate only in engin ...201323853588
oncolytic myxoma virus: the path to clinic.many common neoplasms are still noncurative with current standards of cancer therapy. more therapeutic modalities need to be developed to significantly prolong the lives of patients and eventually cure a wider spectrum of cancers. oncolytic virotherapy is one of the promising new additions to clinical cancer therapeutics. successful oncolytic virotherapy in the clinic will be those strategies that best combine tumor cell oncolysis with enhanced immune responses against tumor antigens. the curren ...201323726825
reverse engineering field isolates of myxoma virus demonstrates that some gene disruptions or loss of function do not explain virulence changes observed in the field.the coevolution of myxoma virus (myxv) and wild european rabbits in australia and europe is a paradigm for the evolution of a pathogen in a new host species. genomic analyses have identified the mutations that have characterized this evolutionary process, but defining causal mutations in the pathways from virulence to attenuation and back to virulence has not been possible. using reverse genetics we examined the role of six selected mutations found in australian field isolates of myxv that fall ...201728768866
apoptosis-inducing effect of myxoma virus on human neuroglioma cell lines.the purpose of this study was to further evaluate the role of myxoma virus (myxv) as an oncolytic agent against experimental human gliomas in vitro, and analyze the effect of myxv on malignant glioma cells at different incubation periods and infected at different multiplicities of infection. neuroglioma cell lines u251 and a172 were cultured with various infective doses of myxoma virus at different time points (0-3 days) and cellular survival rates were evaluated using an mtt assay. cell viabili ...201728672936
myxomatosis in australia and europe: a model for emerging infectious diseases.myxoma virus is a poxvirus naturally found in two american leporid (rabbit) species (sylvilagus brasiliensis and sylvilagus bachmani) in which it causes an innocuous localised cutaneous fibroma. however, in european rabbits (oryctolagus cuniculus) the same virus causes the lethal disseminated disease myxomatosis. the introduction of myxoma virus into the european rabbit population in australia in 1950 initiated the best known example of what happens when a novel pathogen jumps into a completely ...201222333483
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