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human and primate poxviruses: i. growth characteristics of cytolytic and tumor variants.the dual potential of poxviruses to be cytolytic and tumorgenic has been extended. yaba monkey tumor virus formed foci on monkey and human embryonic cells. cytolytic or plaque-forming virus was isolated from yaba tumor homogenates by selective sucrose centrifugation and passage through monkey or human embryonic cells. monkey pox virus (mpv) was cytolytic for monkey cells or human embryonic cells, but upon passage onto young monolayers of human carcinoma cells, hela, produced a restricted cytopat ...1975167685
structural polypeptides of orthopoxvirus: their distribution in various members and location within the virion.the structural polypeptides of accepted species and recently isolated members of the genus orthopoxvirus have been examined by sds-polyacrylamide gel electrophoresis. the viruses shared many polypeptides but some differences were found. the viruses could be divided into a vaccinia group (including buffalopox, 'lenny' and mk-10), an ectromelia group (including elephant virus and moscow virus), cowpox, camelpox and monkeypox. minor differences were found in the polypeptides of monkeypox virus stra ...1979541670
animal poxviruses transmitted from cat to man: current event with lethal end.we report about the infection of an 18-year-old man with an orthopox virus (opv) which was transmitted by a cat. the infectious route from cat to man could be proved by epidemiological, virological and serological methods. the corresponding techniques are described. the patient had not been vaccinated against smallpox and was intensively immunosuppressed by medication on account of a severe endogeneous eczema combined with an allergic asthma bronchiale. a cyclic poxvirus disease developed with a ...19911659066
sequence and evolutionary relationships of african swine fever virus thymidine kinase.the thymidine kinase gene of african swine fever virus was mapped in a 1.4-kb ecori-psti fragment located in the left half of the eco ri k fragment of african swine fever virus dna by using degenerate oligonucleotide probes derived from regions of the thymidine kinase sequence conserved in several poxviruses, man, mouse, and chicken. the nucleotide sequence of this region revealed an open reading frame of 196 codons, whose translated amino acid sequence showed significant similarity to the thymi ...19902389555
stochastic model for interhuman spread of monkeypox.with the eradication of smallpox, systematic routine vaccination with vaccinia has ceased and an increasing proportion of the human population in tropical rain forest areas of central and western africa lacks vaccinia-derived immunity to monkeypox virus. this raises the question of the ability of monkeypox virus to establish and maintain itself in an unvaccinated population through continuous man-to-man transmission. a computerized stochastic model of monte carlo type was constructed to assess t ...19872825518
[monkeys as a source of human viral diseases]. 19852988206
monkeypox virus in relation to the ecological features surrounding human settlements in bumba zone, zaire.since monkeypox virus was discovered in animals in 1958 and in man in 1971, several efforts have been made to identify the reservoir of the virus in nature. in july 1985 a study on human environments and animals suspected to maintain virus transmission was carried out in northern zaire. the study revealed three well demarcated areas: the human settlement area, the agricultural area and the primary tropical rain forest. the first two were found inhabited by terrestrial and arboreal rodents and ba ...19873037740
human monkeypox.between october 1970 and may 1971, six cases of human infection with monkeypox virus were identified in liberia, nigeria, and sierra leone. four of the cases were confirmed by virus isolation and two were diagnosed on the basis of epidemiological and serological investigations. all the cases occurred in unvaccinated individuals.post-infection serological studies showed high haemagglutination-inhibition and neutralizing titres to pox group virus in four of the cases. repeated challenge vaccinatio ...19724340216
isolation and properties of the causal agent of a new variola-like disease (monkeypox) in man.the causal agent of a case of disease in man occurring in the democratic republic of the congo with a similar clinical picture to smallpox was isolated and studied. the agent was identified as monkeypox virus. a comparative study of the isolated strain (congo-8) and of viruses isolated from similar cases of illness in liberia (liberia-1 and liberia-2 strains) and sierra leone (v-70 1 266 strain) showed that they were identical. a number of local species of monkeys and apes were examined serologi ...19724340219
human monkeypox: the past five years. 19846099001
human monkeypox transmitted by a chimpanzee in a tropical rain-forest area of zaire.a case of monkeypox infection in a six-month-old baby girl who had been bitten by a wild chimpanzee in kivu, zaire, was investigated. the child had not been exposed to any monkeypox-like disease and no cases of such disease had occurred in the surrounding area during previous months. the time of onset of rash was consistent with the virus having been transmitted from the chimpanzee. however, it is still not known whether chimpanzees and other primates or lower mammals are the primary reservoir o ...19836132084
[viruses and civilization].a few million years ago, when primates moved from the east african forest to the savannah, they were already infected with endogenous viruses and occultly transmitted them to the prime homo species. however it was much later with the building of the first large cities in mesopotamia that interhuman viral transmission began in earnest. spreading was further enhanced with the organization of the egyptian, greek, roman, and arab empires around the mediterranean. discovery of the new world in 1492 l ...199910901842
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
human monkeypox and smallpox viruses: genomic comparison.monkeypox virus (mpv) causes a human disease which resembles smallpox but with a lower person-to-person transmission rate. to determine the genetic relationship between the orthopoxviruses causing these two diseases, we sequenced the 197-kb genome of mpv isolated from a patient during a large human monkeypox outbreak in zaire in 1996. the nucleotide sequence within the central region of the mpv genome, which encodes essential enzymes and structural proteins, was 96.3% identical with that of vari ...200111734207
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
outbreaks of disease suspected of being due to human monkeypox virus infection in the democratic republic of congo in 2001.seven outbreaks of disease characterized by a pustular rash and suspected to have been caused by human monkeypox virus were investigated. the outbreaks occurred between february and august 2001 in the province of equateur in the democratic republic of congo. the outbreaks involved a total of 31 persons and caused five deaths. specimens from 14 patients were available and were analyzed by electron microscopy, virus isolation, and pcr assays specific for monkeypox virus and varicella-zoster virus. ...200212149352
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
monkeypox transmission and pathogenesis in prairie dogs.during may and june 2003, the first cluster of human monkeypox cases in the united states was reported. most patients with this febrile vesicular rash illness presumably acquired the infection from prairie dogs. monkeypox virus was demonstrated by using polymerase chain reaction in two prairie dogs in which pathologic studies showed necrotizing bronchopneumonia, conjunctivitis, and tongue ulceration. immunohistochemical assays for orthopoxviruses demonstrated abundant viral antigens in surface e ...200415109408
human monkeypox. 200415451482
smallpox vaccine does not protect macaques with aids from a lethal monkeypox virus challenge.it is unknown whether smallpox vaccination would protect human immunodeficiency virus type 1 (hiv-1)-infected individuals, because helper cd4(+) cells, the targets of hiv-1 infection, are necessary for the induction of both adaptive cd8(+) cell and b cell responses. we have addressed this question in macaques and have demonstrated that, although smallpox vaccination is safe in immunodeficient macaques when it is preceded by immunization with highly attenuated vaccinia strains, the macaques were ...200515633096
a tale of two clades: monkeypox viruses.human monkeypox was first recognized outside africa in 2003 during an outbreak in the usa that was traced to imported monkeypox virus (mpxv)-infected west african rodents. unlike the smallpox-like disease described in the democratic republic of the congo (drc; a congo basin country), disease in the usa appeared milder. here, analyses compared clinical, laboratory and epidemiological features of confirmed human monkeypox case-patients, using data from outbreaks in the usa and the congo basin, and ...200516186219
transmission of monkeypox among persons exposed to infected prairie dogs in indiana in 2003.to describe a cluster of human monkeypox cases associated with exposure to ill prairie dogs in a home child care.200516275790
antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection.there is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. for this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called hpmpc ...200616341204
[human monkeypox]. 200717491381
efficacy of therapeutic intervention with an oral ether-lipid analogue of cidofovir (cmx001) in a lethal mousepox model.in the 21st century we are faced with the potential use of natural or recombinant varv and mpxv as biological weapons, and the emergence of human mpxv. such an occurrences would require therapeutic and prophylactic intervention with antivirals. cidofovir, an antiviral approved for the treatment of cytomegalovirus retinitis in aids patients, has activity against poxviruses, but must be administered intravenously and is associated with nephrotoxicity. an ether-lipid analogue of cdv, cmx001 (hdp-cd ...200817904231
clonal vaccinia virus grown in cell culture fully protects monkeys from lethal monkeypox challenge.the potential use of smallpox as an agent of bioterrorism has renewed interest in the development of a modern vaccine capable of replacing the standard dryvax vaccine. vaccinia virus (acam2000), clonally isolated from dryvax and manufactured in cell culture, was tested for immunogenicity and protective activity in a non-human primate model. cynomolgus monkeys vaccinated with acam2000, dryvax, or acam2000 diluent (control) were challenged 2 months post-vaccination with a lethal, intravenous dose ...200818077063
a prairie dog animal model of systemic orthopoxvirus disease using west african and congo basin strains of monkeypox virus.multiple monkeypox virus (mpxv) animal models have been discussed in previous studies, but no small animal models, nor most non-human primate models, demonstrated the protracted asymptomatic incubation phase seen in systemic human orthopoxvirus illness. herein, we characterize a black-tailed prairie dog (pd) (cynomys ludovicianus) model of infection, via intranasal and intradermal exposures, with the two mpxv clades. daily observations of the animals were made (food consumption, general symptoms ...200919141441
st-246 antiviral efficacy in a nonhuman primate monkeypox model: determination of the minimal effective dose and human dose justification.therapeutics for the treatment of pathogenic orthopoxvirus infections are being sought. in the absence of patients with disease, animal models of orthopoxvirus disease are essential for evaluation of the efficacies of antiviral drugs and establishment of the appropriate dose and duration of human therapy. infection of nonhuman primates (nhp) by the intravenous injection of monkeypox virus has been used to evaluate a promising therapeutic drug candidate, st-246. st-246 administered at 3 days post ...200919223621
loop-mediated isothermal amplification-based diagnostic assay for monkeypox virus infections.monkeypox virus (mpxv) causes a smallpox-like disease in non-human primates and humans. this infection is endemic to central and western africa. mpxv is divided into two genetically different groups, congo basin and west african mpxv, with the former being the more virulent. a real-time quantitative mpxv genome amplification system was developed for the diagnosis of mpxv infections using loop-mediated isothermal amplification (lamp) technology. primers used for genome amplification of congo basi ...200919382264
emerging viral infections of the central nervous system: part 1.in this 2-part review, i will focus on emerging virus infections of the central nervous system (cns). part 1 will introduce the basic features of emerging infections, including their definition, epidemiology, and the frequency of cns involvement. important mechanisms of emergence will be reviewed, including viruses spreading into new host ranges as exemplified by west nile virus (wnv), japanese encephalitis (je) virus, toscana virus, and enterovirus 71 (ev71). emerging infections also result fro ...200919667214
application of the ibis-t5000 pan-orthopoxvirus assay to quantitatively detect monkeypox viral loads in clinical specimens from macaques experimentally infected with aerosolized monkeypox virus.monkeypox virus (mpxv), a member of the family poxviridae and genus orthopoxvirus, causes a smallpox-like disease in humans. a previously described pan-orthopoxvirus assay, based on a broad-range polymerase chain reaction (pcr) coupled with electrospray ionization mass spectrometry (pcr/esi-ms), was evaluated for its ability to detect mpxv from spiked human and aerosol-infected cynomolgous macaque (macaca fascicularis) samples. detection of mpxv dna from macaque tissue, blood, and spiked human b ...201020134011
a novel highly reproducible and lethal nonhuman primate model for orthopox virus infection.the intentional re-introduction of variola virus (varv), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. moreover, zoonotic infections with cowpox (cpxv) and monkeypox virus (mpxv) cause severe diseases in humans. smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. the efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. the exis ...201020454688
experimental infection of cynomolgus macaques (macaca fascicularis) with aerosolized monkeypox virus.monkeypox virus (mpxv) infection in humans results in clinical symptoms very similar to ordinary smallpox. aerosol is a route of secondary transmission for monkeypox, and a primary route of smallpox transmission in humans. therefore, an animal model for aerosol exposure to mpxv is needed to test medical countermeasures. to characterize the pathogenesis in cynomolgus macaques (macaca fascicularis), groups of macaques were exposed to four different doses of aerosolized mpxv. blood was collected th ...201020862223
efficacy of cmx001 as a prophylactic and presymptomatic antiviral agent in new zealand white rabbits infected with rabbitpox virus, a model for orthopoxvirus infections of humans.cmx001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (cdv), is being developed as a treatment for smallpox. cmx001 has dramatically increased potency versus cdv against all dsdna viruses and, in contrast to cdv, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. although smallpox has been eliminated from the environment, treatments are urgently being sought due t ...201121369346
Monkeypox disease transmission in an experimental setting: prairie dog animal model.Monkeypox virus (MPXV) is considered the most significant human public health threat in the genus Orthopoxvirus since the eradication of variola virus (the causative agent of smallpox). MPXV is a zoonotic agent endemic to forested areas of Central and Western Africa. In 2003, MPXV caused an outbreak in the United States due to the importation of infected African rodents, and subsequent sequential infection of North American prairie dogs (Cynomys ludovicianus) and humans. In previous studies, the ...201122164263
[tenth anniversary of smallpox eradication: results of epidemiological and virological surveillance and studies in the post-eradication period].in accordance with recommendations of the global commission on the certification of smallpox eradication for the 10-year period after the eradication of this infection, all suspected cases of smallpox have been thoroughly checked up, and in none of them the diagnosis of smallpox has been confirmed. the study of monkeypox in humans has revealed that this zoonosis is spread over a wider area than supposed earlier and covers 7 countries of equatorial africa, occurring most frequently in zaire. in a ...19892552712
quaternary structure of vaccinia virus thymidine kinase.thymidine kinase enzymes isolated from a variety of sources are generally considered to have a native molecular weight of 80-90 kda composed of two 40-45 kda subunits. although these parameters may accurately describe the atypical deoxypyrimidine kinases expressed by members of the herpesviridae, the nucleotide sequences of thymidine kinase genes isolated from human, mouse, chicken and variety of poxviruses (vaccinia virus, monkeypox virus, variola virus, fowlpox virus and capripoxvirus) predict ...19902114104
Status of human monkeypox clinical disease, epidemiology and research.Monkeypox, a vesiculo-pustular rash illness, was initially discovered to cause human infection in 1970 through the World Health Organization (WHO)-sponsored efforts of the Commission to Certify Smallpox Eradication in Western Africa and the Congo Basin. The virus had been discovered to cause a nonhuman primate rash illness in 1958, and was thus named monkeypox. The causative agents of monkeypox and smallpox diseases both are species of Orthopoxvirus. Orthopoxvirus monkeypox, when it infects huma ...201122185831
using remote sensing to map the risk of human monkeypox virus in the congo basin.although the incidence of human monkeypox has greatly increased in central africa over the last decade, resources for surveillance remain extremely limited. we conducted a geospatial analysis using existing data to better inform future surveillance efforts. using active surveillance data collected between 2005 and 2007, we identified locations in sankuru district, democratic republic of congo (drc) where there have been one or more cases of human monkeypox. to assess what taxa constitute the mai ...201021069425
specific inhibition of orthopoxvirus replication by a small interfering rna targeting the d5r gene.concerns about the potential use of smallpox in bioterrorism have stimulated interest in the development of novel antiviral treatments. currently, there are no effective therapies against smallpox and new treatment strategies are greatly needed.200818572748
properties of the recombinant tnf-binding proteins from variola, monkeypox, and cowpox viruses are different.tumor necrosis factor (tnf), a potent proinflammatory and antiviral cytokine, is a critical extracellular immune regulator targeted by poxviruses through the activity of virus-encoded family of tnf-binding proteins (crmb, crmc, crmd, and crme). the only tnf-binding protein from variola virus (varv), the causative agent of smallpox, infecting exclusively humans, is crmb. here we have aligned the amino acid sequences of crmb proteins from 10 varv, 14 cowpox virus (cpxv), and 22 monkeypox virus (mp ...200617070121
human monkeypox--kasai oriental, zaire, 1996-1997.monkeypox is an orthopoxvirus with enzootic circulation in 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 in some cases, death). from february through august 1996, a total of 71 clinical cases of monkeypox, including six deaths, occurred in 13 villages in africa in the katako-kombe health zone (1996 combined population: 15,698), sankuru subregion, kasai or ...19979132583
human monkeypox: a newly emerged orthopoxvirus zoonosis in the tropical rain forests of africa.during the course of the recently concluded smallpox eradication program, a new human orthopoxvirus infection was discovered which is caused by monkeypox virus. the disease occurs sporadically in remote villages within tropical rain forests of west and central africa. the disease is rare; only 155 cases having been reported from 1970 to 1983. the symptoms and signs of human monkeypox resemble those of smallpox, differing significantly only in the occurrence of lymphadenopathy with human monkeypo ...19852992305
human monkeypox: confusion with chickenpox.human monkeypox is a zoonosis occurring sporadically in the tropical rain forest of western and central africa. the exact incidence and geographical distribution are unknown, since many cases are not recognized. special surveillance was established in three regions in zaire in 1981 that led to a substantial increase in reported cases. the question arose as to the possibility that clinical diagnostic errors cause some cases of monkeypox to be misdiagnosed as other eruptive diseases. this paper pr ...19882907258
a protein-based smallpox vaccine protects non-human primates from a lethal monkeypox virus challenge.concerns about infections caused by orthopoxviruses, such as variola and monkeypox viruses, drive ongoing efforts to develop novel smallpox vaccines that are both effective and safe to use in diverse populations. a subunit smallpox vaccine comprising vaccinia virus membrane proteins a33, b5, l1, a27 and aluminum hydroxide (alum) ± cpg was administered to non-human primates, which were subsequently challenged with a lethal intravenous dose of monkeypox virus. alum adjuvanted vaccines provided onl ...201020659519
ecological niche and geographic distribution of human monkeypox in africa.monkeypox virus, a zoonotic member of the genus orthopoxviridae, can cause a severe, smallpox-like illness in humans. monkeypox virus is thought to be endemic to forested areas of western and central africa. considerably more is known about human monkeypox disease occurrence than about natural sylvatic cycles of this virus in non-human animal hosts. we use human monkeypox case data from africa for 1970-2003 in an ecological niche modeling framework to construct predictive models of the ecologica ...200717268575
structure and regulatory profile of the monkeypox inhibitor of complement: comparison to homologs in vaccinia and variola and evidence for dimer formation.the outbreak of monkeypox in the unites states in the summer of 2003 was the first occurrence of this smallpox-like disease outside of africa. this limited human epidemic resulted from cross-infection of prairie dogs by imported african rodents. although there were no human fatalities, this outbreak illustrates that monkeypox is an emerging natural infection and a potential biological weapon. we characterized a virulence factor expressed by monkeypox (monkeypox inhibitor of complement enzymes or ...200616517741
dosage comparison of congo basin and west african strains of monkeypox virus using a prairie dog animal model of systemic orthopoxvirus disease.the prairie dog is valuable for the study of monkeypox virus (mpxv) virulence and closely resembles human systemic orthopoxvirus disease. herein, we utilize a variable dose intranasal challenge with approximately 10(3), 10(4), 10(5), and 10(6)pfu for each clade to further characterize virulence differences between the two mpxv clades. a trend of increased morbidity and mortality as well as greater viral shedding was observed with increasing viral challenge dose. additionally, there appeared to b ...201020374968
experimental infection of an african dormouse (graphiurus kelleni) with monkeypox virus.suitable animal models are needed to study monkeypox virus (mpxv) as human monkeypox clinically resembles smallpox and mpxv is a zoonotic and potential bioterroristic agent. we have demonstrated that a species of african dormice, graphiurus kelleni, is susceptible to a lethal infection of mpxv and that mpxv replicated in multiple organs of this species. following intranasal administration, mpxv replicated locally in the nasal mucosa causing necrosis and hemorrhage with subsequent systemic spread ...200918977501
the highly virulent variola and monkeypox viruses express secreted inhibitors of type i interferon.variola virus (varv) caused smallpox, one of the most devastating human diseases and the first to be eradicated, but its deliberate release represents a dangerous threat. virulent orthopoxviruses infecting humans, such as monkeypox virus (mpxv), could fill the niche left by smallpox eradication and the cessation of vaccination. however, immunomodulatory activities and virulence determinants of varv and mpxv remain largely unexplored. we report the molecular characterization of the varv- and mpxv ...201020019241
comparative analysis of viral gene expression programs during poxvirus infection: a transcriptional map of the vaccinia and monkeypox genomes.poxviruses engage in a complex and intricate dialogue with host cells as part of their strategy for replication. however, relatively little molecular detail is available with which to understand the mechanisms behind this dialogue.200818612436
application of transmission electron microscopy to the clinical study of viral and bacterial infections: present and future.transmission electron microscopy has had a profound impact on our knowledge and understanding of viruses and bacteria. the 1000-fold improvement in resolution provided by electron microscopy (em) has allowed visualization of viruses, the existence of which had previously only been suspected as the causative agents of transmissible infectious disease. viruses are grouped into families based on their morphology. viruses from different families look different and these morphological variances are t ...200616361103
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