Publications

TitleAbstractYear
Filter
PMID(sorted ascending)
Filter
treatment of cowpox virus respiratory infections in mice with ribavirin as a single agent or followed sequentially by cidofovir.to better understand the potential of ribavirin in the treatment of orthopoxvirus infections (such as those acquired through bioterrorist activities), the efficacy of the drug was studied in a cowpox respiratory infection model in mice under varying disease severity. mice did not survive a high intranasal cowpox virus challenge [3 x 10(6) plaque forming units (pfu)/animal] treated with subcutaneous ribavirin (100 mg/kg/day for 5 days), but lived 3.9 days longer than placebos. in contrast, 100% o ...200010950392
intranasal treatment of cowpox virus respiratory infections in mice with cidofovir.orthopoxvirus infections in mice have been effectively treated with cidofovir, a clinically approved drug given by intravenous infusion to treat cytomegalovirus infections. in a bioterrorist scenario it would be technically difficult to give this drug to a large number of exposed individuals. new treatment approaches are being sought, which include giving cidofovir by alternative routes or designing oral prodrugs of cidofovir. in this report, intranasal cidofovir was investigated as a treatment ...200010974369
a longitudinal study of an endemic disease in its wildlife reservoir: cowpox and wild rodents.cowpox is an orthopoxvirus infection endemic in european wild rodents, but with a wide host range including human beings. in this longitudinal study we examined cowpox in two wild rodent species, bank voles clethrionomys glareolus and wood mice apodemus sylvaticus, to investigate the dynamics of a virus in its wild reservoir host. trapping was carried out at 4-weekly intervals over 3 years and each animal caught was uniquely identified, blood sampled and tested for antibodies to cowpox. antibody ...200010982080
detection of poxvirus in cattle associated with human cases in the state of rio de janeiro: preliminary report.this preliminary report describes human and cow cases of poxvirus that recently occurred in the state of rio de janeiro. the electron microscopic findings were consistent with parapoxviral and orthopoxviral infection. orthopoxvirus strains were isolated from human and cow cases. detailed viral characterization by means of genetical techniques is under investigation. based on these informations, poxviral diseases should be also considered an emerging viral zoonosis that can affect human beings.200010998211
an emergent poxvirus from humans and cattle in rio de janeiro state: cantagalo virus may derive from brazilian smallpox vaccine.the biological properties of poxvirus isolates from skin lesions on dairy cows and milkers during recent exanthem episodes in cantagalo county, rio de janeiro state, brazil, were more like vaccinia virus (vv) than cowpox virus. pcr amplification of the hemagglutinin (ha) gene substantiated the isolate classification as an old world orthopoxvirus, and alignment of the ha sequences with those of other orthopoxviruses indicated that all the isolates represented a single strain of vv, which we have ...200011080491
efficacy of 2-amino-7-(1,3-dihydroxy-2-propoxymethyl)purine for treatment of vaccinia virus (orthopoxvirus) infections in mice.we have previously shown that the n-7 substituted acyclic nucleoside analog 2-amino-7-[1,3-dihydroxy-2-propoxy)methyl]purine (compound s2242) is, both in vitro and in animal models, a potent inhibitor of the replication of several herpesviruses (neyts et al., antimicrob. agents chemother. 39:56-60, 1995). here we report on the potent and selective antiviral activity of s2242 against vaccinia virus (vv), an orthopoxvirus. the 50% effective concentrations for inhibition of vv-induced cytopathic ef ...200111120949
detection and differentiation of old world orthopoxviruses: restriction fragment length polymorphism of the crmb gene region.a restriction fragment length polymorphism (rflp) assay was developed to identify and differentiate old world, african-eurasian orthopoxviruses (opv): variola, vaccinia, cowpox, monkeypox, camelpox, ectromelia, and taterapox viruses. the test uses amplicons produced from virus genome dna by pcr with a consensus primer pair designed from sequences determined for the cytokine response modifier b (crmb) gene of 43 different opv strains of known taxonomic origin. the primer pair amplified a single s ...200111136755
orthopoxvirus il-18 binding proteins: affinities and antagonist activities.the affinities of purified recombinant human il-18 binding protein (bp) and ectromelia and cowpox virus homologs for human and murine il-18 were compared by plasmon resonance. the dissociation constants of human il-18bp were similar for murine and human il-18. by contrast, the dissociation constants of the viral proteins for murine il-18 were 12- to 50-fold lower than that for human il-18. the ectromelia and cowpox virus proteins were biologically active, as judged by their ability to inhibit in ...200111145885
an overview of poxviruses.the poxvirus family is a diverse and interesting group of viruses that affect both humans and animals. poxviruses are epitheliotropic and therefore are of interest to the dermatologist. the genera of poxviruses known to affect humans are orthopoxvirus, parapoxvirus, molluscipoxvirus, and yatapoxvirus. the different poxviruses are reviewed, including their history, incidence, clinical presentation, and treatment.200111148468
the immune response to vaccinia virus is significantly reduced after scarification with tk- recombinants as compared to wild-type virus.although it is unlikely that large-scale vaccination against smallpox will ever be required again, it is conceivable that the need may arise to vaccinate against a human orthopoxvirus infection. a possible example could be the emergence of monkey poxvirus (mpv) as a significant human disease in africa. vaccinia virus (vv) recombinants, genetically modified to carry the immunogenic proteins of other pathogenic organisms, have potential use as vaccines against other diseases present in this region ...200011155357
parapoxviruses are strongly inhibited in vitro by cidofovir.three parapoxviruses which cause orf or related diseases in humans and animals and the orthopoxvirus, vaccinia virus, were tested for their in vitro sensitivity to cidofovir. the 50% inhibitory concentration for the three parapoxviruses was between 0.21 and 0.27 microg/ml and for vaccinia was 1.32 microg/ml. the selectivity index varied from 198 to 264 for the parapoxviruses and was 42 for vaccinia virus. virus yield assays confirmed the ability of cidofovir to reduce ortho- and parapoxvirus rep ...200011164507
granzyme a and b-deficient killer lymphocytes are defective in eliciting dna fragmentation but retain potent in vivo anti-tumor capacity.recent studies have demonstrated that granzymes a and b make an important contribution to the clearance of the orthopoxvirus ectromelia, and in graft versus host disease. to test whether granzymes are generally necessary for lymphocyte-mediated cytotoxicity in vivo, we assessed the cytotoxic capacity of granzyme a and/or b-deficient lymphocytes in several perforin-dependent settings. splenocytes and allogeneic ctl of granzyme a and/or b-deficient mice were defective for induction of dna fragment ...200111169436
outbreak of human monkeypox, democratic republic of congo, 1996 to 1997.human monkeypox is a zoonotic smallpox-like disease caused by an orthopoxvirus of interhuman transmissibility too low to sustain spread in susceptible populations. in february 1997, 88 cases of febrile pustular rash were identified for the previous 12 months in 12 villages of the katako-kombe health zone, democratic republic of congo (attack rate = 22 per 1,000; case-fatality rate = 3.7%). seven were active cases confirmed by virus isolation. orthopoxvirus- neutralizing antibodies were detected ...200111384521
the vaccinia virus superoxide dismutase-like protein (a45r) is a virion component that is nonessential for virus replication.a characterization of the a45r gene from vaccinia virus (vv) strain western reserve is presented. the open reading frame is predicted to encode a 125-amino-acid protein (m(r), of 13,600) with 39% amino acid identity to copper-zinc superoxide dismutase (cu-zn sod). sequencing of the a45r gene from other orthopoxviruses, here and by others, showed that the protein is highly conserved in all viruses sequenced, including 16 strains of vv, 2 strains of cowpox virus, camelpox virus, and 4 strains of v ...200111435582
treatment of lethal vaccinia virus respiratory infections in mice with cidofovir.intranasal infection of balb/c mice with the wr strain of vaccinia virus leads to pneumonia, profound weight loss and death. five days after intranasal inoculation, virus from untreated mice was recovered from 11 organs, tissues and whole blood. the highest titres [>10(8) plaque forming units (pfu)/g] were in lungs and nose/sinus tissue, with about 10(7) pfu/g in spleen and blood. seven other organs contained 30- to > or = 50-fold lower amounts of virus. mice infected with the related cowpox vir ...200111437324
poxviruses and the origin of the eukaryotic nucleus.a number of molecular forms of dna polymerases have been reported to be involved in eukaryotic nuclear dna replication, with contributions from alpha-, delta-, and epsilon-polymerases. it has been reported that delta-polymerase possessed a central role in dna replication in archaea, whose ancestry are thought to be closely related to the ancestor of eukaryotes. indeed, in vitro experiment shown here suggests that delta-polymerase has the potential ability to start dna synthesis immediately after ...200111443345
cowpox virus in a 12-year-old boy: rapid identification by an orthopoxvirus-specific polymerase chain reaction.although smallpox was eradicated 20 years ago, other members of the genus orthopoxvirus (opv), such as cowpox virus (cpxv) or monkeypox virus, are still a threat to humans. because human cpxv infection is rare, it is seldom suspected on clinical grounds only. we report a boy who presented with two necrotic ulcers with surrounding erythema. infection with opv was suspected, as antibiotic treatment had not produced improvement and smears were negative for anthrax. an opv was isolated and an opv-sp ...200111453925
cowpox virus and other members of the orthopoxvirus genus interfere with the regulation of nf-kappab activation.nf-kappab comprises a family of transcription factors that regulate key immune processes. in this study, the effects of orthopoxvirus infection upon the activation of nf-kappab were examined. during the early phase of infection, cowpox virus can inhibit the induction of nf-kappab-regulated gene expression by interfering with the process of ikappabalpha degradation. although either okadaic acid or tumor necrosis factor (tnf) treatment of infected cells can induce ikappabalpha phosphorylation, fur ...200111543670
[isolation and identification of the smallpox virus which caused iatrogenic vaccinia in children in the city of vladivostok].the comparative study of the specimens of the morphological elements of exanthema obtained from 8 children with the clinical diagnosis of secondary exogenic vaccinia, dried smallpox vaccine and the cultures of other orthopoxviruses (rabbit pox, monkey pox and buffalo pox viruses) was made. the isolation and identification of the causative agents from the specimens was carried out with the use of modern virological, electron microscopic and molecular methods. the study proved the fact that 8 chil ...200111548257
species-specific differences in the organization of the complement-binding protein of orthopoxviruses. 200111605339
species-specific differences in the structure of orthopoxvirus complement-binding protein.vaccinia virus complement-binding protein (vcp) is secreted from the cells infected with the virus and controls the complement activation reactions. this protein contains four short consensus repeats (scr), typical of the protein family of complement activation regulators. organization of the vcp genes/proteins of orthopoxviruses-monkeypox (mpv), variola, cowpox and vaccinia viruses-and their cellular homologues (daf and c4bp) were studied comparatively. for this purpose, vcp genes of three mpv ...200111682123
characterization of a vaccinia-like virus isolated in a brazilian forest.the span232 virus (spanv) was isolated from sentinel mice in the forest of cotia, são paulo, brazil. it was grouped originally as a cotia virus (cv) sample due to serological cross-reaction with the latter. however, spanv presented genetic characteristics that differed from cv and indicated that spanv is a member of the vaccinia virus (vv) subgroup. spanv showed a hindiii-digested dna pattern similar to those of the wr and lister strains of vv. also, spanv presented genes homologous to the vacci ...200211752719
comparison of closely related orthopoxvirus isolates by random amplified polymorphic dna and restriction fragment length polymorphism analysis.the reliability and reproducibility of random amplified polymorphic dna analysis (rapd) was compared with restriction fragment length polymorphism (rflp) by analysing three virus strains isolated from zoo animals in berlin and three isolates which were cultivated from pets from northern germany. the rapd technique was evaluated as a reliable tool with good reproducibility of the patterns for each virus strain investigated. problems of interpretation due to inconsistent intensity of bands in diff ...200111765800
inhibition of interferons by ectromelia virus.ectromelia virus (ev) is an orthopoxvirus (opv) that causes mousepox, a severe disease of laboratory mice. mousepox is a useful model of opv infection because ev is likely to be a natural mouse pathogen, unlike its close relatives vaccinia virus (vv) and variola virus. several studies have highlighted the importance of mouse interferons (ifns) in resistance to and recovery from ev infection, but little is known of the anti-ifn strategies encoded by the virus itself. we have determined that 12 di ...200211773388
characterization of ati, tk and ifn-alpha/betar genes in the genome of the bean 58058 virus, a naturally attenuated wild orthopoxvirus.the lack of knowledge about the natural host of vaccinia virus (vv) along with the description of human infections caused by poxviruses after smallpox eradication has increased the need to characterize poxviruses isolated from the wild. moreover, in the past years poxviruses have been widely studied as potential vaccination tools, with the discovery of several genes implicated in the evasion of the host immune response involved in virus pathogenesis. among them, an interferon (ifn)-binding prote ...200111778697
species-level identification of orthopoxviruses with an oligonucleotide microchip.a method for species-specific detection of orthopoxviruses pathogenic for humans and animals is described. the method is based on hybridization of a fluorescently labeled amplified dna specimen with the oligonucleotide dna probes immobilized on a microchip (magichip). the probes identify species-specific sites within the crmb gene encoding the viral analogue of tumor necrosis factor receptor, one of the most important determinants of pathogenicity in this genus of viruses. the diagnostic procedu ...200211880388
enhanced inhibition of orthopoxvirus replication in vitro by alkoxyalkyl esters of cidofovir and cyclic cidofovir.the nucleotide phosphonates cidofovir (cdv) and cyclic cidofovir (ccdv) are potent antiviral compounds when administered parenterally but are not well absorbed orally. these compounds have been reported to have activity against orthopoxvirus replication in vitro and in animal models when administered parenterally or by aerosol. to obtain better oral activity, we synthesized a novel series of analogs of cdv and ccdv by esterification with two long-chain alkoxyalkanols, 3-hexadecyloxy-1-propanol ( ...200211897580
structural analysis of the extracellular domain of vaccinia virus envelope protein, a27l, by nmr and cd spectroscopy.this study presents the molecular structure of the extracellular domain of vaccinia virus envelope protein, a27l, determined by nmr and cd spectroscopy. a recombinant protein, ea27l-aa, containing this domain in which cysteines 71 and 72 were replaced with alanine, was constructed to prevent self-assembly due to intermolecular disulfide bonds between these two cysteines. the soluble ea27l-aa protein forms an oligomer resembling that of a27l on vaccinia virions. heteronuclear correlation nmr spec ...200211901147
the sequence of camelpox virus shows it is most closely related to variola virus, the cause of smallpox.camelpox virus (cmpv) and variola virus (var) are orthopoxviruses (opvs) that share several biological features and cause high mortality and morbidity in their single host species. the sequence of a virulent cmpv strain was determined; it is 202182 bp long, with inverted terminal repeats (itrs) of 6045 bp and has 206 predicted open reading frames (orfs). as for other poxviruses, the genes are tightly packed with little non-coding sequence. most genes within 25 kb of each terminus are transcribed ...200211907336
amplification of 'variola virus-specific' sequences in german cowpox virus isolates.in 1995 a polymerase chain reaction (pcr) protocol describing the specific detection of variola virus, the causative agent of smallpox, was published by knight and others. virulent variola major strains could be differentiated from less virulent variola minor strains because of the distinct amplicon sizes. here, we applied this pcr protocol to dna from various orthopoxvirus isolates. there was no amplification with the orthopoxvirus species vaccinia, monkeypox, mousepox, or camelpox viruses. how ...200211911586
characterization of wild-type and cidofovir-resistant strains of camelpox, cowpox, monkeypox, and vaccinia viruses.cidofovir ([(s)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine] [hpmpc])-resistant forms of camelpox, cowpox, monkeypox, and vaccinia viruses were developed by prolonged passage in vero 76 cells in the presence of drug. eight- to 27-fold-higher concentrations of cidofovir were required to inhibit the resistant viruses than were needed to inhibit the wild-type (wt) viruses. resistant viruses were characterized by determining their cross-resistance to other antiviral compounds, examining their di ...200211959564
[smallpox]. 200111980393
the zoonotic poxviruses.animal poxviruses occasionally produce human skin disease often associated with systemic illness. lesions are painful blisters and crusted eschars and are usually self-limiting and rarely fatal. treatment is generally supportive.200212017086
antiviral activity and mode of action studies of ribavirin and mycophenolic acid against orthopoxviruses in vitro.two inhibitors of cellular inosine monophosphate dehydrogenase, mycophenolic acid (mpa) and ribavirin, were evaluated for inhibitory activity against orthopoxviruses. unrelated antipoxvirus agents tested for comparison included 6-azauridine, cidofovir (hpmpc) and cyclic hpmpc. mpa inhibited camelpox, cowpox, monkeypox and vaccinia viruses by 50% in plaque reduction assays at 0.2-3 microm in african green monkey kidney (vero 76) and mouse 3t3 cells. ribavirin was considerably more active in 3t3 c ...200112018677
species-specific differences in organization of orthopoxvirus kelch-like proteins.organization of orthopoxvirus proteins of the kelch superfamily and their genes were analyzed and compared. complete genomic sequences of variola (var), monkeypox (mpv), vaccinia (vac), and species-specific regions of cowpox (cpv) viruses were used in the work. despite the multiplicity of kelch-like proteins in orthopoxviruses, their function is still vague. it has been discovered that the genes of orthopoxvirus kelch-like proteins are localized only to the terminal variable regions of the genom ...200212018707
orthologs of the vaccinia a13l and a36r virion membrane protein genes display diversity in species of the genus orthopoxvirus.alignment of vaccinia and variola virus genomes has highlighted some targets that display diversity. we have investigated the sequence diversity of two viral membrane protein genes from 36 different orthopoxvirus (opv) strains to evaluate the suitability of these loci to differentiate between opv species. orthologs of the vaccinia virus copenhagen a13l gene were all predicted to have functional genes that ranged between 201-213 bps in length. whereas the n- and c-termini of each protein were rel ...200212021869
the genome of camelpox virus.camelpox virus (cmlv), a member of the orthopoxvirus genus in the poxviridae, is the etiologic agent of a disease of camels. here we report the cmlv genomic sequence with analysis. the 205,719-bp cmlv genome contains 211 putative genes and consists of a central region bound by identical inverted terminal repeats of approximately 7 kb. a high degree of similarity in gene order, gene content, and amino acid composition in the region located between cmlv017 and cmlv184 (average 96% amino acid ident ...200212033760
variola virus immune evasion design: expression of a highly efficient inhibitor of human complement.variola virus, the most virulent member of the genus orthopoxvirus, specifically infects humans and has no other animal reservoir. variola causes the contagious disease smallpox, which has a 30-40% mortality rate. conversely, the prototype orthopoxvirus, vaccinia, causes no disease in immunocompetent humans and was used in the global eradication of smallpox, which ended in 1977. however, the threat of smallpox persists because clandestine stockpiles of variola still exist. although variola and v ...200212034872
cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: a soluble, secreted cd30 homologue.cowpox virus (brighton red strain) possesses one of the largest genomes in the orthopoxvirus genus. sequence analysis of a region of the genome that is type-specific for cowpox virus identified a gene, vcd30, encoding a soluble, secreted protein that is the fifth member of the tumor necrosis factor receptor family known to be encoded by cowpox virus. the vcd30 protein contains 110 aa, including a 21-residue signal peptide, a potential o-linked glycosylation site, and a 58-aa sequence sharing 51- ...200212034885
detection of smallpox virus dna by lightcycler pcr.a 300-bp plasmid fragment of the hemagglutinin gene was used as target dna to develop a rapid real-time lightcycler (roche applied science, indianapolis, ind.) pcr assay for laboratory detection of smallpox virus. pcr primers and probes were designed specifically for detection of smallpox virus dna, but all viruses of the genus orthopoxvirus tested could be detected by use of the hemagglutinin gene target sequence. base pair mismatches in the 204-bp amplicon allowed discrimination of cowpox viru ...200212037052
apoptosis during ectromelia orthopoxvirus infection is devdase dependent: in vitro and in vivo studies.ectromelia virus (ev), which causes mousepox, is a member of the orthopoxviruses that are defined as being able to suppress apoptosis. caspase-3 is one of the key effector proteases which regulates the apoptotic cascade and which is responsible for dna fragmentation observed during apoptosis. it is well known that viruses, especially poxviruses, can inhibit caspase activity. here, we report that ev can regulate apoptosis in vitro, suppressing the activity of caspases recognizing the devd (asp-gl ...200212048029
species-specific differences in the organization of genes encoding kelch-like proteins of orthopoxviruses pathogenic for humans. 200212058374
treatment of lethal cowpox virus respiratory infections in mice with 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine and its orally active diacetate ester prodrug.the acyclic purine nucleoside analog, 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (s2242) and its orally active diacetate ester prodrug (hoe961) were reported to be potent inhibitors of vaccinia virus replication in cell culture and in infected mice. these compounds were evaluated further, using infections with the related cowpox virus. against a wild-type (wt) cowpox virus strain in mouse c127i cell culture, 50% effective concentrations (ec(50), determined by plaque reduction assays) of s ...200212062396
analysis of the monkeypox virus genome.monkeypox virus (mpv) belongs to the orthopoxvirus genus of the family poxviridae, is endemic in parts of africa, and causes a human disease that resembles smallpox. the 196,858-bp mpv genome was analyzed with regard to structural features and open reading frames. each end of the genome contains an identical but oppositely oriented 6379-bp terminal inverted repetition, which similar to that of other orthopoxviruses, includes a putative telomere resolution sequence and short tandem repeats. compu ...200212083817
[orthopoxvirus genes for kelch-like proteins. i. analysis of species specific differences by gene structure and organization].genes and proteins of the kelch superfamily were structurally analyzed in the smallpox (spv), monkeypox (mpv), cowpox (cpv), and vaccinia (vv) viruses. genes potentially coding for the kelch-like proteins were found only in the variable terminal regions of the orthopoxvirus genome. the set and sizes of their protein products varied with species. all genes of the superfamily proved to be disrupted by mutations in spv, which is highly pathogenic for its only host, man. the largest set of kelch-lik ...200212173463
effect of 5-iodo-2'-deoxyuridine on vaccinia virus (orthopoxvirus) infections in mice.there is a concern that there may be unregistered stocks of smallpox that can be used for bioterrorism or biological warfare. according to the who advisory committee on variola research, there is a need to develop strategies to treat smallpox infections should they reappear. it would also be important to have an effective drug at hand for the treatment of monkeypox disease in humans. we show here that 5-iodo-2'-deoxyuridine (idu) is a potent inhibitor of vaccinia virus (vv) replication and that ...200212183236
the interaction of orthopoxviruses and interferon-treated cultured cells. 200212205783
an investigation of incorporation of cellular antigens into vaccinia virus particles.vaccinia virus (vv) infection produces several types of virus particle called intracellular mature virus (imv), intracellular enveloped virus (iev), cell-associated enveloped virus (cev) and extracellular enveloped virus (eev). some cellular antigens are associated with eev and these vary with the cell type used to grow the virus. to investigate if specific cell antigens are associated with vv particles, and to address the origin of membranes used to envelope imv and iev/cev/eev, we have studied ...200212237415
identification of the orthopoxvirus p4c gene, which encodes a structural protein that directs intracellular mature virus particles into a-type inclusions.the orthopoxvirus gene p4c has been identified in the genome of the vaccinia virus strain western reserve. this gene encodes the 58-kda structural protein p4c present on the surfaces of the intracellular mature virus (imv) particles. the gene is disrupted in the genome of cowpox virus brighton red (br), demonstrating that although the p4c protein may be advantageous for virus replication in vivo, it is not essential for virus replication in vitro. complementation and recombination analyses with ...200212388681
spectrum of antimicrobial activity and user acceptability of the hand disinfectant agent sterillium gel.the antimicrobial efficacy of alcohol-based hand gels has been shown to be significantly less than liquid hand rubs probably because of a lower concentration of alcohol. sterillium gel is the first hand gel with 85% ethanol. its antimicrobial efficacy and user acceptability was studied. bactericidal activity was tested according to pren 12054 against staphylococcus aureus, enterococcus hirae, pseudomonas aeruginosa and escherichia coli (suspension test) and en 1500 (15 volunteers; four replicate ...200212392906
antiviral activity of cyclopentenyl nucleosides against orthopox viruses (smallpox, monkeypox and cowpox).an improved method for the synthesis of enantiomerically pure d-cyclopentenyl nucleosides has been accomplished and their antiviral activity against orthopox viruses have been evaluated. the key intermediate, l-cyclopent-2-enone 13 was prepared from d-ribose using a ring closing metathesis reaction in eight steps. among the synthesized nucleosides, the adenine 2 (neplanocin a), cytosine 14, and 5-f-cytosine 15 analogues exhibited potent anti-orthopox virus activity, including smallpox virus.200312467606
[smallpox, bioterrorism agent].a considerable risk: among the infectious agents that might be used as terrorist weapons, the smallpox virus represents a sufficiently high risk, which is difficult to manage and must be seriously taken into account. from a microbiological point of view: two viral strains of the smallpox virus, which belong to the poxviridae and orthopoxvirus-type families, are known. they are associated with various clinical presentations of smallpox, i.e., variola major and variola minor or "alastrim". variola ...200212497725
identification of vaccinia virus epitope-specific hla-a*0201-restricted t cells and comparative analysis of smallpox vaccines.despite worldwide eradication of naturally occurring variola virus, smallpox remains a potential threat to both civilian and military populations. new, safe smallpox vaccines are being developed, and there is an urgent need for methods to evaluate vaccine efficacy after immunization. here we report the identification of an immunodominant hla-a*0201-restricted epitope that is recognized by cytotoxic cd8(+) t cells and conserved among orthopoxvirus species including variola virus. this finding has ...200312518065
images in clinical medicine. cowpox infection. 200312556545
araçatuba virus: a vaccinialike virus associated with infection in humans and cattle.we describe a vaccinialike virus, araçatuba virus, associated with a cowpoxlike outbreak in a dairy herd and a related case of human infection. diagnosis was based on virus growth characteristics, electron microscopy, and molecular biology techniques. molecular characterization of the virus was done by using polymerase chain reaction amplification, cloning, and dna sequencing of conserved orthopoxvirus genes such as the vaccinia growth factor (vgf), thymidine kinase (tk), and hemagglutinin. we u ...200312603984
[identification of orthopoxvirus species using oligonucleotide micro-chips].a method for describing the orthopoxviruses that are pathogenic both to man and animals is described in the article. the method is based on hybridization of a fluorescently labelled amplified dna sample with oligonucleotides, which were immobilized in a microchip. species-specific regions within the crmb gene encoding a viral analogue of the tumor necrosis factor receptor, i.e. an important gene determining the pathogenicity of the mentioned orthopoxviruses type, were used as a target for identi ...200312608052
potential antiviral therapeutics for smallpox, monkeypox and other orthopoxvirus infections.we assessed the activities of 24 different antiviral compounds against smallpox (two strains of variola major and one of variola minor), monkeypox, vaccinia and cowpox viruses by a neutral red uptake assay. to establish assay parameters, we examined viral replication and its inhibition at various times postinfection and at several multiplicities of infection. drugs were selected to target a range of functions involved in viral replication. eight compounds (cidofovir, cyclic hpmpc (chpmpc), hpmpa ...200312615299
in vitro activity of potential anti-poxvirus agents.the potential use of variola or another orthopoxvirus such as monkeypox as a weapon of bioterrorism has stimulated efforts to develop new drugs for treatment of smallpox or other poxvirus infections. at the present time only cidofovir is approved for use in the emergency treatment of smallpox outbreaks. although cidofovir is very active against the orthopoxviruses in vitro and in animal model infections, it is not active when given orally and must be administered with precaution so as to avoid r ...200312615301
a review of compounds exhibiting anti-orthopoxvirus activity in animal models.several animal models using mice (most frequently), rabbits, or monkeys have been used to identify compounds active against orthopoxvirus infections. the treatment of vaccinia virus infections has been well studied in models involving infection of scarified skin or eyes, or resulting from intravenous, intraperitoneal, intracerebral, or intranasal virus inoculation. cowpox virus has been used in intranasal or aerosol infection studies to evaluate the treatment of lethal respiratory infections. ra ...200312615302
four-gene-combination dna vaccine protects mice against a lethal vaccinia virus challenge and elicits appropriate antibody responses in nonhuman primates.two major infectious forms of vaccinia virus (vacv) have been described: the intracellular mature virion (imv), and the extracellular enveloped virion (eev). due to their stability in the environment, imvs play a predominant role in host-to-host transmission, whereas eevs play an important role in dissemination within the host. in a previous report, we demonstrated that mice vaccinated with vacv l1r (imv immunogen) and a33r (eev immunogen) were protected from a lethal poxvirus challenge. vaccina ...200312620810
[immunomodulatory proteins of orthopoxviruses].the review considers recent data on the structural-functional organization of the genome of orthopoxviruses pathogenic for humans, including the variola, monkeypox, cowpox, and vaccinia viruses. emphasis was placed on the structure of molecular virulence factors that suppress the inflammatory reactions, immune response, and interferon effects induced by virus infection.200312624944
administration of vaccinia virus to mice may cause contact or bedding sentinel mice to test positive for orthopoxvirus antibodies: case report and follow-up investigation.routine testing of bedding sentinels from a barrier room revealed one mouse seropositive to ectromelia virus (ev). results of hemagglutination-inhibition testing and western blot analysis were confirmatory for orthopoxvirus antibodies. additional seropositive animals were not identified. interviews indicated that replication-competent vaccinia virus (vv), western reserve strain (vv-wr), recently had been given to mice. although vv-wr was not expected to spread by contact or via fomites, the case ...200312625512
human monkeypox in kasai oriental, zaire (1996-1997).monkeypox is an orthopoxvirus with enzootic circulation in the rainforests of central and western africa; the virus can be transmitted to humans and cause a syndrome clinically similar to smallpox (e.g., pustular rash, fever, respiratory symptoms, and in199712631813
[multiplex pcr analysis for species specific express-identification of orthopoxviruses].a method for one-stage rapid identification of the four orthopovirus species, which are pathogenic to humans, involving multiplex polymerase chain reaction (mpcr) was developed. five pairs of oligonucleotides primers were simultaneously used in the mentioned mpcr assay of orthopoxvirus dna; one of the pairs was genus-specific, the remaining four primers were species-specific for variola, monkey-pox, cowpox and vaccine-pox. the specificity and sensitivity of the developed method were evaluated th ...200312656047
accidental infection of laboratory worker with vaccinia virus.we report the accidental needlestick inoculation of a laboratory worker with vaccinia virus. although the patient had previously been vaccinated against smallpox, severe lesions appeared on the fingers. western blot and polymerase chain reaction-restriction fragment length polymorphism were used to analyze the virus recovered from the lesions. the vaccinia virus-specific immunoglobulin g levels were measured by enzyme-linked immunosorbent assay. our study supports the need for vaccination for la ...200312781015
multistate outbreak of monkeypox--illinois, indiana, and wisconsin, 2003.cdc has received reports of patients with a febrile rash illness who had close contact with pet prairie dogs and other animals. the marshfield clinic, marshfield, wisconsin, identified a virus morphologically consistent with a poxvirus by electron microscopy of skin lesion tissue from a patient, lymph node tissue from the patient's pet prairie dog, and isolates of virus from culture of these tissues. additional laboratory testing at cdc indicated that the causative agent is a monkeypox virus, a ...200312803191
high-frequency genetic recombination and reactivation of orthopoxviruses from dna fragments transfected into leporipoxvirus-infected cells.poxvirus dna is not infectious because establishing an infection requires the activities of enzymes packaged in the virion. this barrier can be overcome by transfecting virus dna into cells previously infected with another poxvirus, since the resident virus can provide the trans-acting systems needed to reactivate transfected dna. in this study we show that cells infected with a leporipoxvirus, shope fibroma virus (sfv), can reactivate vaccinia virus dna. similar heterologous packaging systems w ...200312805426
comparative effects of cidofovir and cyclic hpmpc on lethal cowpox and vaccinia virus respiratory infections in mice.cidofovir is approved for the treatment of cytomegalovirus retinitis in humans. although highly effective, the drug can cause renal toxicity in patients. there is much interest in cidofovir as a potential treatment for smallpox, monkeypox and other orthopoxvirus infections. a cyclic phosphonate form of cidofovir, 1-[((s)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosine (cyclic hpmpc), was reported to be less nephrotoxic than cidofovir in animals. thus, it was deemed important to dire ...200312815205
evaluation of nucleoside phosphonates and their analogs and prodrugs for inhibition of orthopoxvirus replication.in the event of a bioterrorism attack using smallpox virus, there currently is no approved drug for the treatment of infections with this virus. we have reported previously that (s)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (hpmpc) (also known as cidofovir [cdv]) has good activity against poxvirus infections; however, a major limitation is the requirement for intravenous administration. two related acyclic nucleoside phosphonates (anps), adefovir (pmea) and tenofovir (pmpa), are active ag ...200312821467
ocular complications of smallpox vaccination.to describe the ocular complications of smallpox vaccination and to discuss potential therapeutic options.200312888060
real-time pcr assay to detect smallpox virus.we developed a highly sensitive and specific assay for the rapid detection of smallpox virus dna on both the smart cycler and lightcycler platforms. the assay is based on taqman chemistry with the orthopoxvirus hemagglutinin gene used as the target sequence. with genomic dna purified from variola virus bangladesh 1975, the limit of detection was estimated to be approximately 25 copies on both machines. the assay was evaluated in a blinded study with 322 coded samples that included genomic dna fr ...200312904397
[the study of orthopoxvirus genes for kelch-like proteins. ii. construction of cowpox virus variants with targeted gene deletions].integrative plasmids p delta c, p delta d, and p delta g were designed to contain a selective marker beyond the region of homology to virus dna and to allow construction of recombinant cowpox viruses (cpv) that lack c18l, d11l, or g3l coding for kelch-like proteins. cpv mutants lacking one (c18l, d11l, or g3l), two (d11l/g3l or c18l/d11l), or three (d11l/g3l/c18l, that is, all) kelch-like protein genes of the left variable region of the virus genome were obtained. impaired reproduction was obser ...200312942630
detection and discrimination of orthopoxviruses using microarrays of immobilized oligonucleotides.variola virus (varv), causing smallpox, is a potential biological weapon. methods to detect varv rapidly and to differentiate it from other viruses causing similar clinical syndromes are needed urgently. we have developed a new microarray-based method that detects simultaneously and discriminates four orthopoxvirus (opv) species pathogenic for humans (variola, monkeypox, cowpox, and vaccinia viruses) and distinguishes them from chickenpox virus (varicella-zoster virus or vzv). the opv gene c23l/ ...200312951214
smallpox: residual antibody after vaccination.of all the microorganisms and toxins, poxviruses (orthopoxvirus) have the greatest potential for use by terrorists. these viruses can spread rapidly through the environment following initial infection. in 1980, the world health organization eradication program discontinued vaccination for smallpox and declared that the disease had been eliminated. with the threat of smallpox virus as a bioterrorism weapon, questions have been asked about the persistence of protection (as offered by antibodies) f ...200312958227
comparative assessment of the properties of orthopoxviral soluble receptors for tumor necrosis factor. 200312959070
development of a candidate polyvalent live vaccine against human immunodeficiency, hepatitis b, and orthopox viruses. 200312959074
feline orthopoxvirus infection transmitted from cat to human.we report the case of a 56-year-old female patient who presented with an inflamed, ulcerated lesion on the left side of her neck after contact (scratch) with a cat living in the patient's house. satellite lesions developed despite local treatment and parenteral clindamycin. histopatholgic examination and the tzanck test showed evidence of a viral infection. subsequent transmission electron microscopy of scrap tissue and material from a fresh pustule exhibited multiple typical poxvirus particles, ...200312963921
on-the-job exposure to hiv. 200314503166
viral infections in atopic dermatitis: pathogenic aspects and clinical management.a number of different widespread and disseminated viral infections can occur in patients with atopic dermatitis. eczema molluscatum is troublesome but not dangerous. although eczema vaccinatum is rare, it is life-threatening and of increased concern as smallpox vaccinations are reintroduced as a response to possible bioterrorism. there is little information on the course of smallpox itself in atopic dermatitis. eczema herpeticum is the most common member of this group; recent advances in underst ...200314564342
practical synthesis of d- and l-2-cyclopentenone and their utility for the synthesis of carbocyclic antiviral nucleosides against orthopox viruses (smallpox, monkeypox, and cowpox virus).highly efficient and practical methodology for the syntheses of d- and l-4,5-o-isopropylidene-2-cyclopentenone (9 and 22), versatile intermediates for the synthesis of carbocyclic nucleosides, have been developed via a ring-closing metathesis reaction from d-ribose in eight steps. the utility of d- and l-4,5-o-isopropylidene-2-cyclopentenone is demonstrated by their application for the preparation of d-cyclopentyl-6-azauridine 12 and d-cyclopentenyl-5-halocytosine nucleosides (33-35) using mitsu ...200314604375
electron microscopy and the investigation of new infectious diseases.to review and assess the role of electron microscopy in the investigation of new infectious diseases.200314656415
analysis of an orf virus chemokine-binding protein: shifting ligand specificities among a family of poxvirus viroceptors.we identify a secreted chemokine inhibitor encoded by orf virus (orfv), the prototypic poxvirus of the parapoxvirus genus, and show that it is related to the poxvirus type ii cc-chemokine-binding proteins (cbp-ii) produced by members of the orthopoxvirus and leporipoxvirus genera. the orfv chemokine-binding protein (cbp) is functionally similar to the cbp-ii proteins in its ability to bind and inhibit many cc-chemokines with high affinity. however, unlike cbp-ii, the orfv cbp also binds with hig ...200314657392
identification of polymorphic tandem repeats by direct comparison of genome sequence from different bacterial strains: a web-based resource.polymorphic tandem repeat typing is a new generic technology which has been proved to be very efficient for bacterial pathogens such as b. anthracis, m. tuberculosis, p. aeruginosa, l. pneumophila, y. pestis. the previously developed tandem repeats database takes advantage of the release of genome sequence data for a growing number of bacteria to facilitate the identification of tandem repeats. the development of an assay then requires the evaluation of tandem repeat polymorphism on well-selecte ...200414715089
cowpox with severe generalized eruption, finland.cowpox with a severe, generalized eruption was diagnosed in an atopic 4-year-old girl by electron microscopy, virus isolation, polymerase chain reaction, and immunoglobulin (ig) m and low-avidity igg antibodies. the hemagglutinin gene of the isolate clustered with a russian cowpox virus strain, and more distantly, with other cowpox and vaccinia virus strains. the patient's dog had orthopoxvirus-specific antibodies, indicating a possible transmission route. in finnish wild rodents, orthopoxvirus ...200314718092
flow cytometry and t-cell response monitoring after smallpox vaccination.orthopoxvirus zoonosis or smallpox as result of bioterrorism or biological warfare represents a risk for epidemic spread. by monitoring t-cell responses by flow cytometry, we observed a recall response after recent vaccination against smallpox. when the high similarity between the orthopoxviruses is considered, this rapid assay that uses vaccinia antigens could identify recently exposures.200314718095
poxvirus genomes: a phylogenetic analysis.the evolutionary relationships of 26 sequenced members of the poxvirus family have been investigated by comparing their genome organization and gene content and by using dna and protein sequences for phylogenetic analyses. the central region of the genome of chordopoxviruses (chpvs) is highly conserved in gene content and arrangement, except for some gene inversions in fowlpox virus (fpv) and species-specific gene insertions in fpv and molluscum contagiosum virus (mcv). in the central region 90 ...200414718625
human monkeypox: an emerging zoonosis.human monkeypox is a rare viral zoonosis endemic to central and western africa that has recently emerged in the usa. laboratory diagnosis is important because the virus can cause disease that is clinically indistinguishable from other pox-like illnesses, particularly smallpox and chickenpox. although the natural animal reservoir of the monkeypox virus is unknown, rodents are the probable source of its introduction into the usa. a clear understanding of the virulence and transmissibility of human ...200414720564
oral treatment of cowpox and vaccinia virus infections in mice with ether lipid esters of cidofovir.four newly synthesized ether lipid esters of cidofovir (cdv), hexadecyloxypropyl-cdv (hdp-cdv), octadecyloxyethyl-cdv (ode-cdv), oleyloxypropyl-cdv (olp-cdv), and oleyloxyethyl-cdv (ole-cdv), were found to have enhanced activities against vaccinia virus (vv) and cowpox virus (cv) in vitro compared to those of cdv. the compounds were administered orally and were evaluated for their efficacies against lethal cv or vv infections in mice. hdp-cdv, ode-cdv, and ole-cdv were effective at preventing mo ...200414742188
smallpox and pan-orthopox virus detection by real-time 3'-minor groove binder taqman assays on the roche lightcycler and the cepheid smart cycler platforms.we designed, optimized, and extensively tested several sensitive and specific real-time pcr assays for rapid detection of both smallpox and pan-orthopox virus dnas. the assays are based on taqman 3'-minor groove binder chemistry and were performed on both the rapid-cycling roche lightcycler and the cepheid smart cycler platforms. the hemagglutinin (ha) j7r, b9r, and b10r genes were used as targets for the variola virus-specific assays, and the ha and dna polymerase-e9l genes were used as targets ...200414766823
rapid detection and differentiation of human pathogenic orthopox viruses by a fluorescence resonance energy transfer real-time pcr assay.the orthopox viruses that are pathogenic for humans include variola major virus (var), monkeypox virus (mpv), cowpox virus (cpv), and to a lesser extent, camelpox virus (cml) and vaccinia virus (vac). pcr is a powerful tool to detect and differentiate orthopox viruses, and real-time pcr has the further advantages of rapid turnaround time, low risk of contamination, capability of strain differentiation, and use of multiplexed probes.200414962998
efficacy of oral active ether lipid analogs of cidofovir in a lethal mousepox model.cidofovir (cdv) is a highly effective inhibitor of orthopoxvirus replication and may be used intravenously to treat smallpox or complications arising from the smallpox vaccine under an investigational new drug application (ind). however, cdv is absorbed poorly following oral administration and is inactive orally. to improve the bioavailability of cdv, others synthesized alkoxyalkanol esters of cdv and observed >100-fold more activity than unmodified cdv against cowpox, vaccinia, and variola viru ...200414972516
detection of orthopoxvirus dna by real-time pcr and identification of variola virus dna by melting analysis.although variola virus was eradicated by the world health organization vaccination program in the 1970s, the diagnosis of smallpox infection has attracted great interest in the context of a possible deliberate release of variola virus in bioterrorist attacks. obviously, fast and reliable diagnostic tools are required to detect variola virus and to distinguish it from orthopoxviruses that have identical morphological characteristics, including vaccinia virus. the advent of real-time pcr for the c ...200415004077
laboratory confirmation of generalized vaccinia following smallpox vaccination.the reinitiation of smallpox vaccination has renewed interest in implementing modern diagnostic methods to assess orthopoxvirus infection and adverse events following vaccination. we report here the laboratory confirmation of vaccinia virus in pustular lesions of a healthy adult vaccinee by use of a two-tier algorithm incorporating taqman pcr and electron microscopy.200415004124
amplification refractory mutation system pcr assays for the detection of variola and orthopoxvirus.pcr assays that can identify the presence of variola virus (varv) sequences in an unknown dna sample were developed using principles established for the amplification refractory mutation system (arms). the assay's specificity utilised unique single nucleotide polymorphisms (snp) identified among orthopoxvirus (opv) orthologs of the vaccinia virus copenhagen strain a13l and a36r genes. when a variola virus specific primer was used with a consensus primer in an arms assay with different orthopoxvi ...200415019263
[phylogenetic analysis of chemokine-binding protein gene from orthopoxviruses].poxviruses, belonging to the genus of orthopoxviruses and leporipoxviruses, express a protein that binds a wide spectrum of cc-chenokines. the above viral protein (vcci) has no homology by the amino acid sequence with the known cellular receptors of chemokines or with any other proteins represented in databases. sixty-nine nucleotide sequences of the vcci protein gene of 4 orthopoxviruses, which are pathogenic to man, and of 2 species, to whom man is immune, as well as 16 of such sequences borro ...200415025002
prevention of lethal respiratory vaccinia infections in mice with interferon-alpha and interferon-gamma.the antiviral efficacy of interferons (ifns) was evaluated using a vaccinia intranasal infection model in mice in this study. we provide evidence that intranasal administration of ifn-alpha and ifn-gamma (days -1 to +3) resulted in 100 and 90% survival against a lethal respiratory vaccinia infection (8 ld50) in mice, respectively; whereas no animals in the placebo group survived through the study period (21 days). the ifn treatment consisted of a single daily dose of 5x10(3) u per mouse for 5 co ...200415039095
anti-cowpox virus activities of certain adenosine analogs, arabinofuranosyl nucleosides, and 2'-fluoro-arabinofuranosyl nucleosides.nucleoside analogs were investigated for their potential to inhibit cowpox virus (a surrogate for variola and monkeypox viruses) in cell culture and in lethal respiratory infections in mice. cell culture antiviral activity was determined by plaque reduction assays, with cytotoxicity determined by cell proliferation assays. selectivity indices (si's, 50% cytotoxic concentration divided by 50% virus-inhibitory concentration) were determined for 15 compounds. three arabinofuranosyl (ara) nucleoside ...200415043161
viral appropriation of apoptotic and nf-kappab signaling pathways.viruses utilize a variety of strategies to evade the host immune response and replicate in the cells they infect. the comparatively large genomes of the orthopoxviruses and gammaherpesviruses encode several immunomodulatory proteins that are homologous to component of the innate immune system of host cells, which are reviewed here. however, the viral mechanisms used to survive host responses are quite distinct between these two virus families. poxviruses undergo continuous lytic replication in t ...200415048867
[cowpox virus infection in a child].although human cowpox virus infection is rare nowadays, an animal reservoir of this virus still exists. the general course of cowpox virus infections is usually benign but the diagnosis is difficult and often late. case report: an 11-year-old boy, owner of two cats, presented with an infected sacral wound lesion associated with fever and lymph nodes. the wound became necrotic and other cutaneous and mucous membrane lesions developed secondarily. blood tests did not show hyperleukocytosis or a sy ...200415051092
bioterrorism and emerging infectious disease - antimicrobials, therapeutics and immune-modulators. viral infections. 200415057646
Displaying items 201 - 300 of 700