Publications

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crystallization and preliminary x-ray analysis of the chemokine-binding protein from orf virus (poxviridae).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 p ...201020606282
mouse cd8alpha+ dcs and human bdca3+ dcs are major producers of ifn-lambda in response to poly ic.polyinosinic:polycytidylic acid (poly ic), a double-stranded rna, is an effective adjuvant in vivo. ifn-λs (also termed il-28/29) are potent immunomodulatory and antiviral cytokines. we demonstrate that poly ic injection in vivo induces large amounts of ifn-λ, which depended on hematopoietic cells and the presence of tlr3 (toll-like receptor 3), irf3 (ifn regulatory factor 3), irf7, ifn-i receptor, fms-related tyrosine kinase 3 ligand (fl), and irf8 but not on myd88 (myeloid differentiation fact ...201020975040
novel deer-associated parapoxvirus infection in deer hunters.parapoxviruses are a genus of the double-stranded dna family of poxviruses that infect ruminants, and zoonotic transmission to humans often results from occupational exposures. parapoxvirus infection in humans begins with an incubation period of 3 to 7 days, followed by the development of one or more erythematous maculopapular lesions that evolve over the course of several weeks into nodules. in 2009, parapoxvirus infection was diagnosed in two deer hunters in the eastern united states after the ...201021190456
molecular and biological characterization of vascular endothelial growth factor of parapoxviruses isolated from wild japanese serows (capricornis crispus).contagious dermatitis in domestic and wild ruminants caused by parapoxvirus (ppv) occurs worldwide. although ppv infections appear in cattle, sheep and goats, the papular, nodular, pustular and ulcerated skin lesions of wild japanese serows (capricornis crispus) are significantly more severe than those of other animals. to determine the factors involved in the severity of these skin lesions, we compared the molecular characteristics of 4 ppv isolates from japanese serows and 2 isolates from shee ...201019716664
specific antibodies induced by inactivated parapoxvirus ovis potently enhance oxidative burst in canine blood polymorphonuclear leukocytes and monocytes.we have recently shown that inactivated parapoxvirus ovis (ippvo) effectively stimulates canine blood phagocytes. however, a potential link between innate and adaptive immunity induced by ippvo remained open. the objective of this study was to define the effects of repeated ippvo treatment of dogs to evaluate (i) ippvo-specific antibody production, and (ii) modulation of ippvo-induced oxidative burst by anti-ippvo antibodies. serum analysis of dogs treated repeatedly with ippvo (zylexis) showed ...201019748192
multicolour, multiplex real-time pcr assay for the detection of human-pathogenic poxviruses.after eradication of variola virus, one of the most dangerous infectious diseases affecting mankind, today other poxviruses of different genera can cause infection in humans. these viruses include human-specific molluscipoxviruses as well as zoonotic orthopoxviruses and parapoxviruses. while non-variola orthopoxvirus infections mostly cause mild symptoms in immunocompetent persons, they can evoke severe disease in immunocompromised patients. since the typical poxviral skin lesions are rarely dia ...201019879351
diagnosis and phylogenetic analysis of orf virus from goats in china: a case report.orf virus (orfv) is the etiological agent of contagious pustular dermatitis and is the prototype of the genus parapoxvirus (ppv). it causes a severe exanthematous dermatitis that afflicts domestic and wild small ruminants.201020416112
effects of two commercially available immunostimulants on leukocyte function of foals following ex vivo exposure to rhodococcus equi.the objective of this study was to determine the effect of immunostimulants on neutrophil, macrophage, and lymphocyte function following ex vivo exposure to rhodococcus equi. eighteen foals were randomly assigned to one of 3 treatment groups. treatment consisted of inactivated propionibacterium acnes (pa), inactivated parapoxvirus ovis (ppvo), or saline (control) administered on days 0 (7 days of age), 2, and 8. bronchoalveolar lavage (bal) fluid and blood were collected on days 0 (baseline), 12 ...201020822815
a man with an umbilicated papule of the hand: what is your diagnosis?introduction. ecthyma contagiosum is a zoonotic disease caused by the parapoxvirus that causes "sore mouth" in sheep and goats and orf in human. case presentation. a 61-year-old sheep farmer presented with a painful non-pruritic lesion on the left hand that had been present for approximately 5 weeks. physical examination demonstrated a 1 cm pearly, umbilicated papule with raised borders. a biopsy showed an asymmetrical nodule with parakeratotic crust and acanthosis with thin epidermal strands ex ...201020585366
phylogenetic analysis of croatian orf viruses isolated from sheep and goats.the orf virus (orfv) is the prototype of the parapoxvirus genus and it primarily causes contagious ecthyma in goats, sheep, and other ruminants worldwide. in this paper, we described the sequence and phylogenetic analysis of the b2l gene of orfv from two natural outbreaks: i) in autochthonous croatian cres-breed sheep and ii) on small family goat farm.201021073725
orf virus orfv121 encodes a novel inhibitor of nf-kappab that contributes to virus virulence.orf virus (orfv), the type member of the genus parapoxvirus of the poxviridae, has evolved novel strategies (proteins and/or mechanisms of action) to modulate host cell responses regulated by the nuclear factor-κb (nf-κb) signaling pathway. here, we present data indicating that orfv orfv121, a gene unique to parapoxviruses, encodes a novel viral nf-κb inhibitor that binds to and inhibits the phosphorylation and nuclear translocation of nf-κb-p65. the infection of cells with an orfv121 deletion m ...201021177808
tissue damage caused by animal orthopoxviruses cowpox, ectromelia, vaccinia and parapoxvirus ovis in human cornea. 201019878105
identification and phylogenetic analysis of an orf virus isolated from an outbreak in sheep in the jilin province of china.this study investigated an acute outbreak of contagious ecthyma dermatitis that occurred in november 2008 in a herd of 180 small-tailed han sheep in the jilin province of china. the pathological findings of this case revealed severe vascular proliferation, viral cytopathic changes in keratinocytes by vacuolar degeneration, ballooning degeneration, and eosinophilic cytoplasmic inclusions, suggesting that the disease could have been caused by an orf virus (orfv) infection. immunohistochemistry, in ...201019948384
diagnosis of bovine-associated parapoxvirus infections in humans: molecular and epidemiological evidence.orf virus, pseudocowpox virus and bovine papular stomatitis virus, are parapoxviruses, associated with domestic ruminants, which are capable of causing cutaneous infections in humans. owing to virtually identical appearances in humans, clinical differentiation of these viruses is difficult. we discuss three recent occurrences of parapoxvirus infection, involving contact with domestic bovine and use a combination of molecular and epidemiological data in the diagnosis. these cases underscore the u ...201020163577
molecular and virological studies on contagious pustular dermatitis isolates from egyptian sheep and goats.orf virus was clinically diagnosed from different field cases of sheep and goat in hawamdia, giza, egypt during the summer 2006. skin scabs were collected and used for virus isolation, electron microscopy, pcr and sequencing for confirmation, and differential diagnosis. the aetiological virus was fruitfully isolated on the chorio-allantoic membrane of spf embryonated chicken eggs indicated by expressing the characteristic pock lesions of poxviridae family. electron microscopy examination exposed ...201020304450
the genome of pseudocowpoxvirus: comparison of a reindeer isolate and a reference strain.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, re ...201020107016
parapoxvirus infections of red deer, italy.to characterize parapoxviruses causing severe disease in wild ruminants in stelvio park, italy, we sequenced and compared the dna of several isolates. results demonstrated that the red deer isolates are closely related to the parapox of red deer in new zealand virus.201121470460
effects of inactivated parapoxvirus ovis on the cumulative incidence of pneumonia and cytokine secretion in foals on a farm with endemic infections caused by rhodococcus equi.the objectives of the present study were to determine if administration of inactivated parapoxvirus ovis (ippvo) can decrease the cumulative incidence of pneumonia and increase the number of ifn-?- and il-4-secreting cells among foals. fifty-nine foals were randomly assigned to 2 treatment groups (ippvo or placebo) prior to birth. at 24-48 h of age, foals received 2 ml of either ippvo or a placebo by intramuscular injection. injections were repeated 24h and 8 days later. the number of ifn-?- and ...201121255847
investigation and analysis of a human orf outbreak among people living on the same farm.human orf is a viral zoonotic infection caused by parapoxvirus. the skin lesions of human orf can be misdiagnosed as cutaneous anthrax leading to overtreatment and also fear. this study was conducted to analyze an outbreak which led to deaths among kids and lambs in the same flock, and skin lesions in some persons who were living on the same farm that were initially diagnosed as cutaneous anthrax by a practitioner. eight patients with skin lesions and eleven persons who had no skin lesion were c ...201121344145
characterization of immunostimulatory components of orf virus (parapoxvirus ovis).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-? 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 pr ...201121346027
analysis of deletion within the reindeer pseudocowpoxvirus genome.cases of contagious pustular stomatitis have been reported in finnish reindeer for many years. two species of the genus parapoxvirus of the family poxviridae have been identified as the causative agent of the disease; orf virus (orfv) was found during the 1992-1993 epidemic and pseudocowpoxvirus (pcpv) was connected to the 1999-2000 epidemic. the genome of reindeer parapoxvirus from the latter outbreak, isolate f00.120r, was recently sequenced and confirmed as pcpv. the six gene deletion of the ...201121798294
validation of a high-throughput real-time polymerase chain reaction assay for the detection of capripoxviral dna.capripoxviruses, which are endemic in much of africa and asia, are the aetiological agents of economically devastating poxviral diseases in cattle, sheep and goats. the aim of this study was to validate a high-throughput real-time pcr assay for routine diagnostic use in a capripoxvirus reference laboratory. the performance of two previously published real-time pcr methods were compared using commercially available reagents including the amplification kits recommended in the original publication. ...201122138682
inactivated orf virus (parapoxvirus ovis) induces antitumoral activity in transplantable tumor models.orf virus (orfv, parapoxvirus ovis) possesses strong immunomodulating activity including the induction of interferon gamma (ifn-γ) and interleukin-12 (il-12) expression. antiviral effects have been described which appeared to be facilitated by an orfv-induced type 1 helper t-cell (th1-type) immune response. in this study, we investigated the potential antitumoral activity of inactivated orfv in transplantable tumor models. we show that parenteral administration of inactivated orfv mediates antit ...201122199278
severe oesophagitis in an adult bull caused by bovine papular stomatitis virus. 201121926143
a new recombinant orf virus (orfv, parapoxvirus) protects rabbits against lethal infection with rabbit hemorrhagic disease virus (rhdv).this report describes the generation of a new recombinant orf virus (orfv; parapoxvirus) expressing the major capsid protein vp1 (vp60) of the calicivirus, rabbit hemorrhagic disease virus (rhdv). authentic expression of vp1 could be demonstrated in cells infected with the recombinant d1701-v-vp1 without the need for production of infectious orfv progeny. notably, infected cells also released empty calicivirus-like particles (vlps). challenge experiments showed that even a single immunization wi ...201122001119
Generation of recombinant Orf virus using an enhanced green fluorescent protein reporter gene as a selectable marker.ABSTRACT: BACKGROUND: Reporter genes are often used as a selectable marker for generation of recombinant viruses in order to investigate the mechanism of pathogenesis and to obtain candidate vaccine viruses. Routine selection of the recombinant parapoxvirus is time-consuming and labor intensive. Therefore, developing a novel method for selection is critical. RESULTS: In this study, we developed a rapid method to generate recombinant Orf viruses (ORFV) based on the enhanced green fluorescent p ...201122192523
genus specific evolution of codon usage and nucleotide compositional traits of poxviruses.poxviruses are complex in their nucleotide compositional features of the coding regions. the codon usages in poxviruses are in accordance with their compositional bias. in the poxviridae family, codon usage patterns and nucleotide compositional traits are widely divergent across species but some conservation was observed within a genus. viruses from six chordopox genera, i.e., avipoxvirus, capripoxvirus, cervidpoxvirus, orthopoxvirus, suipoxvirus, yatapoxvirus, and one entomopox genus- betaentom ...201121369827
orf parapoxvirus infection from a cat scratch.a 53-year-old woman presented with an enlarging, tender, ulcerated nodule on her dorsal hand after being scratched by a stray kitten. histology was consistent with orf parapoxvirus infection. the lesion resolved without scarring after several weeks of treatment with imiquimod 5 percent cream. orf is a zoonosis transmitted to humans from sheep and goats by direct contact or by fomites. transmission by cat scratch has not been previously described in the literature.201121549084
Zoonotic transmission of bovine papular stomatitis virus. 201121873394
molecular analysis of parapoxvirus from a spotted seal phoca largha in japan.a spotted seal phoca largha with nodular and scab lesions on the whole body was brought to an aquarium in nagoya, japan. we extracted dna from the lesions and used the polymerase chain reaction (pcr) method for detecting orthopoxvirus and parapoxvirus dna. parapoxvirus but not orthopoxvirus dna was detected. the partial nucleotide sequence of the envelope gene was determined from the pcr product, and the sequence was seen to be closely related to 2 parapoxvirus strains from spotted seals in alas ...201122235590
orfv: a novel oncolytic and immune stimulating parapoxvirus therapeutic.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 develop ...201222273579
novel immune-modulator identified by a rapid, functional screen of the parapoxvirus ovis (orf virus) genome.abstract: background: the success of new sequencing technologies and informatic methods for identifying genes has made establishing gene product function a critical rate limiting step in progressing the molecular sciences. we present a method to functionally mine genomes for useful activities in vivo, using an unusual property of a member of the poxvirus family to demonstrate this screening approach. results: the genome of parapoxvirus ovis (orf virus) was sequenced, annotated, and then used to ...201222243932
phylogenetic analysis of strains of orf virus isolated from two outbreaks of the disease in sheep in greece.abstract: background: although orf is endemic around the world, there are few descriptions of orf virus strains and comparisons of these strains. we report the sequence and phylogenetic analysis of the partial b2l gene of orf virus from two outbreaks of the disease in greece. the first was an outbreak of genital form of the disease in a flock imported from france, whilst the second was an outbreak of the disease in the udder skin of ewes and around the mouth of lambs in an indigenous flock. res ...201222260526
Development of orf virus as a bifunctional recombinant vaccine: Surface display of Echinococcus granulosus antigen EG95 by fusion to membrane structural proteins.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 h ...201222085551
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