Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| 5-(dimethoxymethyl)-2'-deoxyuridine: a novel gem diether nucleoside with anti-orthopoxvirus activity. | to provide potential new leads for the treatment of orthopoxvirus infections, the 5-position of the pyrimidine nucleosides have been modified with a gem diether moiety to yield the following new nucleosides: 5-(dimethoxymethyl)-2'-deoxyuridine (2b), 5-(diethoxymethyl)-2'-deoxyuridine (3b), 5-formyl-2'-deoxyuridine ethylene acetal (4b), and 5-formyl-2'-deoxyuridine propylene acetal (5b). these were evaluated in human foreskin fibroblast cells challenged with the vaccinia virus or cowpox virus. of ... | 2006 | 16722657 |
| detection of monkeypox virus with real-time pcr assays. | human monkeypox, a zoonotic disease, was first reported outside of africa during the 2003 us outbreak. | 2006 | 16731033 |
| poxvirus cd8+ t-cell determinants and cross-reactivity in balb/c mice. | mouse models of orthopoxvirus disease provide great promise for probing basic questions regarding host responses to this group of pathogens, which includes the causative agents of monkeypox and smallpox. however, some essential tools for their study that are taken for granted with other mouse models are not available for these viruses. here we map and characterize the initial cd8+ t-cell determinants for poxviruses in h-2d-haplotype mice. cd8+ t cells recognizing these three determinants make up ... | 2006 | 16775319 |
| obligatory requirement for antibody in recovery from a primary poxvirus infection. | to understand the correlates of protective immunity against primary variola virus infection in humans, we have used the well-characterized mousepox model. this is an excellent surrogate small-animal model for smallpox in which the disease is caused by infection with the closely related orthopoxvirus, ectromelia virus. similarities between the two infections include virus replication and transmission, aspects of pathology, and development of pock lesions. previous studies using ectromelia virus h ... | 2006 | 16775322 |
| recombinant human polyclonal antibodies: a new class of therapeutic antibodies against viral infections. | the mammalian immune system eliminates pathogens by generating a specific antibody response. polyclonality is a key feature of this immune response: the immune system produces antibodies which bind to different structures on a given pathogen thereby increasing the likelihood of its elimination. the vast majority of current recombinant antibody drugs rely on monospecific monoclonal antibodies. inherently, such antibodies do not represent the benefits of polyclonality utilized by a natural immune ... | 2006 | 16787244 |
| activities of alkoxyalkyl esters of cidofovir (cdv), cyclic cdv, and (s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine against orthopoxviruses in cell monolayers and in organotypic cultures. | the potencies of several alkoxyalkyl esters of acyclic nucleoside phosphonates against vaccinia virus and cowpox virus were evaluated in cell monolayers and three-dimensional epithelial raft cultures. prodrugs were at least 20-fold more active than their parent compounds. octadecycloxyethyl-(s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine emerged as the most potent derivative. | 2006 | 16801436 |
| toward orthopoxvirus countermeasures: a novel heteromorphic nucleoside of unusual structure. | two privileged drug scaffolds have been hybridized to create the novel heteromorphic nucleoside 5-(2-amino-3-cyano-5-oxo-5,6,7,8-tetrahydro-4h-chromen-4-yl)-1-(2-deoxypentofuranosyl)pyrimidine-2,4(1h,3h)-dione (2). compound 2 inhibited the replication of two orthopoxviruses, vaccinia virus (vv) (ec(50) = 4.6 +/- 2.0 microm), and cowpox virus (cv) (ec(50) = 2.0 +/- 0.3 microm). compound 2 exhibited reduced activity against a thymidine kinase (tk) negative strain of cv, implying a requirement for ... | 2006 | 16821766 |
| detection and identification of orthopoxviruses using a generic nested pcr followed by sequencing. | some orthopoxviruses are considered to be potential biological weapons. after the smallpox eradication campaign ended, routine vaccination was stopped around the world. consequently, a significant portion of the population is now completely unprotected from infection by variola virus and related orthopoxviruses. some of the symptoms associated with non-variola infections can be similar to smallpox, causing alert and panic situations. these infections should be considered as real public health co ... | 2006 | 16872000 |
| monkeypox: an epidemiologic and clinical comparison of african and us disease. | monkeypox is a double-stranded dna virus and a member of the genus orthopoxvirus. human monkeypox was first identified in the democratic republic of the congo (formerly zaire) in 1970. the first outbreak in the western hemisphere occurred in the spring of 2003. important epidemiologic and clinical differences exist between human monkeypox in the united states and in africa, including sex distribution, case fatality, morphology of skin lesions, and associated lymphadenopathy. these divergent clin ... | 2006 | 16908354 |
| poxviral regulation of the host nf-kappab response: the vaccinia virus m2l protein inhibits induction of nf-kappab activation via an erk2 pathway in virus-infected human embryonic kidney cells. | exposure of eukaryotic cells to viruses will activate the host nf-kappab transcription factor, resulting in proinflammatory and immune protein production. vaccinia virus (vv), the prototypic orthopoxvirus, expresses products that inhibit this antiviral event. to identify novel mechanisms responsible for this effect, we made use of a vv deletion mutant (mva) that stimulates nf-kappabeta activation in infected 293t cells. in this virus-host system, the extents of nf-kappabeta-regulated gene expres ... | 2006 | 16912315 |
| a case of facial cellulitis and necrotizing lymphadenitis due to cowpox virus infection. | we describe a patient with facial cellulitis/erysipelas due to cowpox virus inoculation in the respiratory epithelium of the nose. a cytopathic agent was isolated in cell culture, and the diagnosis of cowpox was confirmed by electron microscopy and polymerase chain reaction. the most likely source of infection was exposure to the family cats. in addition to the severe edematous cellulitis of the face, the clinical course was dominated by several areas of subcutaneous, necrotizing lymphadenitis, ... | 2006 | 16912948 |
| microarray assay for detection and discrimination of orthopoxvirus species. | a microarray method was developed for simultaneous detection and identification of six species of orthopoxvirus (opv) including variola, monkeypox, cowpox, camelpox, vaccinia, and ectromelia viruses. the method allowed us to discriminate opv species from varicella-zoster virus (vzv), herpes simplex 1 virus (hsv-1), and herpes simplex 2 virus (hsv-2) that cause infections with clinical manifestations similar to opv infections. the nucleotide sequences of the c23l/b29r and the b19r genes identifie ... | 2006 | 16927285 |
| the unique c termini of orthopoxvirus gamma interferon binding proteins are essential for ligand binding. | the orthopoxviruses ectromelia virus (ectv) and vaccinia virus (vacv) express secreted gamma interferon binding proteins (ifn-gammabps) with homology to the ligand binding domains of the host's ifn-gamma receptor (ifn-gammar1). homology between these proteins is limited to the extracellular portions of the ifn-gammar1 and the first approximately 200 amino acids of the ifn-gammabps. the remaining 60 amino acids at the c termini of the ifn-gammabps contain a single cysteine residue shown to be imp ... | 2006 | 16928759 |
| genome of horsepox virus. | here we present the genomic sequence of horsepox virus (hspv) isolate mnr-76, an orthopoxvirus (opv) isolated in 1976 from diseased mongolian horses. the 212-kbp genome contained 7.5-kbp inverted terminal repeats and lacked extensive terminal tandem repetition. hspv contained 236 open reading frames (orfs) with similarity to those in other opvs, with those in the central 100-kbp region most conserved relative to other opvs. phylogenetic analysis of the conserved region indicated that hspv is clo ... | 2006 | 16940536 |
| solution structure of the complex between poxvirus-encoded cc chemokine inhibitor vcci and human mip-1beta. | chemokines (chemotactic cytokines) comprise a large family of proteins that recruit and activate leukocytes, giving chemokines a major role in both immune response and inflammation-related diseases. the poxvirus-encoded viral cc chemokine inhibitor (vcci) binds to many cc chemokines with high affinity, acting as a potent inhibitor of chemokine action. we have used heteronuclear multidimensional nmr to determine the structure of an orthopoxvirus vcci in complex with a human cc chemokine, mip-1bet ... | 2006 | 16963564 |
| short-term, but not post-exposure, protection against lethal orthopoxvirus challenge after immunization with modified vaccinia virus ankara. | safety-tested vaccinia virus (vacv) mva serves as a candidate third-generation vaccine against smallpox. here, mva immunization of mice shortly before or after lethal respiratory challenge with vacv western reserve was investigated. whilst post-exposure treatment failed to protect animals, immunizations on day 2 prior to challenge were fully protective. on the day of challenge, mva inoculation may prevent death, but not onset of severe respiratory disease. after intranasal mva application, massi ... | 2006 | 16963750 |
| cidofovir resistance in vaccinia virus is linked to diminished virulence in mice. | cidofovir [(s)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (hpmpc)] is recognized as a promising drug for the treatment of poxvirus infections, but drug resistance can arise by a mechanism that is poorly understood. we show here that in vitro selection for high levels of resistance to hpmpc produces viruses encoding two substitution mutations in the virus dna polymerase (e9l) gene. these mutations are located within the regions of the gene encoding the 3'-5' exonuclease (a314t) and polymeras ... | 2006 | 16973545 |
| vaccinia virus infection attenuates innate immune responses and antigen presentation by epidermal dendritic cells. | langerhans cells (lcs) are antigen-presenting cells in the skin that play sentinel roles in host immune defense by secreting proinflammatory molecules and activating t cells. here we studied the interaction of vaccinia virus with xs52 cells, a murine epidermis-derived dendritic cell line that serves as a surrogate model for lcs. we found that vaccinia virus productively infects xs52 cells, yet this infection displays an atypical response to anti-poxvirus agents. whereas adenosine n1-oxide blocke ... | 2006 | 17005676 |
| short communication inhibitory activity of 4-[(1,2-dihydro-2-oxo-3h-indol-3-ylidene)amino]-n-(4,6-dimethylpyrimidin-2-yl) benzenesulphonamide and its derivatives against orthopoxvirus replication in vitro. | 4-[(1,2-dihydro-2-oxo-3h-indol-3-ylidene)amino]-n-(4,6-dimethylpyrimidin-2-yl) benzenesulphonamide and its derivatives were tested in vitro for antiviral activity against vaccinia and cowpox virus replication in human foreskin fibroblast (hff) cells, and their activity was compared with cidofovir (cdv). among the tested compounds, 4-[(5-methyl-1,2-dihydro-2-oxo-3-h-indol-3-ylidene)amino]-n-(4,6-dimethylpyrimidin-2-yl)benzene-sulphonamide was the most active against vaccinia virus, with a 50% eff ... | 2006 | 17042332 |
| use of internally controlled real-time genome amplification for detection of variola virus and other orthopoxviruses infecting humans. | smallpox, once a devastating disease caused by variola virus, a member of the orthopoxvirus genus, was eradicated in 1980. however, the importance of variola virus infections has been stressed widely in the last few years, particularly following recent social events in the world. today, variola virus is considered to be one of the most significant agents with potential use as a biological weapon. in this study we developed an internally controlled real-time pcr assay for rapid detection and simu ... | 2006 | 17065259 |
| 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 ... | 2006 | 17070121 |
| the vaccinia virus protein f1l interacts with bim and inhibits activation of the pro-apoptotic protein bax. | vaccinia virus, the prototypic member of the orthopoxvirus genus, encodes the mitochondrial-localized protein f1l that functions to protect cells from apoptotic death and inhibits cytochrome c release. we previously showed that f1l interacts with the pro-apoptotic bcl-2 family member bak and inhibits activation of bak following an apoptotic stimulus (wasilenko, s. t., banadyga, l., bond, d., and barry, m. (2005) j. virol. 79, 14031-14043). in addition to bak, the pro-apoptotic protein bax is als ... | 2006 | 17074758 |
| raccoonpox in a canadian cat. | poxvirus infections affecting the skin of cats are extremely rare in north america, in contrast to europe where cowpox virus is well recognized as an accidental pathogen in cats that hunt small rodents. the virus or viruses responsible for the anecdotal cases in north america have never been characterized. this paper reports a case of raccoonpox infection in a canadian cat. biopsy of the initial ulcerative lesion on the forepaw revealed ballooning degeneration of surface and follicular keratinoc ... | 2006 | 17083577 |
| serological survey for viral pathogens in turkish rodents. | wild rodents (n = 330) were trapped around the villages of altindere and coşandere (maçka, trabzon province), ayder, ortan, and yolkiyi (camlihemşin, rize province), and bozdag (odemiş, izmir province) in northeastern and western turkey during april 2004. samples were tested for arenavirus, hantavirus, and cowpox virus (family poxviridae, genus orthopoxvirus, cpxv) antibodies by using immunofluorescence assays (ifas). antibodies against arenaviruses were found in eight of 330 (2.4%) rodents. are ... | 2006 | 17092901 |
| [an oligonucleotide microarray for detection and discrimination of orthopoxviruses based on oligonucleotide sequences of two viral genes]. | an oligonucleotide microarray for detection and identification of orthopoxviruses was developed. genus specific and orthopoxvirus species-specific regions of the genes encoding chemokine binding and alpha/beta-interferon binding proteins were used as a target. the developed microarray allows the variola, monkeypox, cowpox, vaccinia, camel-pox and ectromelia (mousepox) viruses to be distinguished with a high degree of reliability. | 2006 | 17094655 |
| a protein-based smallpox vaccine protects mice from vaccinia and ectromelia virus challenges when given as a prime and single boost. | the heightened concern about the intentional release of variola virus has led to the need to develop safer smallpox vaccines. while subunit vaccine strategies are safer than live virus vaccines, subunit vaccines have been hampered by the need for multiple boosts to confer optimal protection. here we developed a protein-based subunit vaccine strategy that provides rapid protection in mouse models of orthopoxvirus infections after a prime and single boost. mice vaccinated with vaccinia virus envel ... | 2007 | 17098336 |
| efficacy of delayed treatment with st-246 given orally against systemic orthopoxvirus infections in mice. | st-246 was evaluated for activity against cowpox virus (cv), vaccinia virus (vv), and ectromelia virus (ectv) and had an in vitro 50% effective concentration (ec50) of 0.48 microm against cv, 0.05 microm against vv, and 0.07 microm against ectv. the selectivity indices were >208 and >2,000 for cv and vv, respectively. the in vitro antiviral activity of st-246 was significantly greater than that of cidofovir, which had an ec50 of 41.1 microm against cv and 29.2 microm against vv, with selectivity ... | 2007 | 17116683 |
| [entomopoxviruses and biological control.] | poxviridae are divided into two subfamilies: the chordopoxvirinae (poxviruses of vertebrates) and the entomopoxvirinae (insect poxviruses). entomopoxviruses (epvs) are large (300-400 nm) oval shaped viruses. the genome of epvs is large, with covalent ends and is a linear double-stranded dna (200-240 kbp) molecule. the entomopoxvirinae comprises three genera based on host insect and virion morphology. genus a viruses infect coleopterans, genus b viruses infect lepidopterans and orthopterans, and ... | 2005 | 17124689 |
| comparative study of pathological changes in the mouse viscera in infection caused by two orthopoxviruses. | the mechanisms of infection development in intraperitoneal inoculation of mice by ectromelia virus strain k-1 and cowpox strain ep-2 were studied. ultrastructural parameters of virus assembly and maturation are described. differences in the types of cells replicating the viruses and in the type of visceral injuries were detected. the studies showed a local type of strain ep-2 cowpox infection and dissemination of ectromelia strain k-1. | 2006 | 17152368 |
| smallpox vaccines: past, present, and future. | the global eradication of smallpox was a tremendous achievement made possible by the development of an effective vaccine. routine vaccination of the general population is no longer recommended. however, stocks of variola virus, the causative agent of smallpox, still exist in 2 secure laboratories, and permanent disposal has been controversial. in addition, there is speculation that variola virus may exist outside of these 2 facilities, and there is a concern that the threat of smallpox will be u ... | 2006 | 17157663 |
| identification of residues in the ectromelia virus gamma interferon-binding protein involved in expanded species specificity. | gamma interferon (ifn-gamma) production is important in the host response to, and recovery from, infection with ectromelia virus (ectv) and vaccinia virus (vacv). the orthopoxviruses have evolved several mechanisms to subvert the ifn-gamma response. ifn-gamma-binding protein (ifn-gammabp) is a virally encoded homologue of the host ifn-gamma receptor that blocks the effects of ifn-gamma in the infected host. unlike the cellular receptors, whose ligand specificity is restricted to their own specie ... | 2007 | 17170436 |
| from actually toxic to highly specific--novel drugs against poxviruses. | the potential use of variola virus, the causative agent of smallpox, as a bioweapon and the endemic presence of monkeypox virus in africa demonstrate the need for better therapies for orthopoxvirus infections. chemotherapeutic approaches to control viral infections have been less successful than those targeting bacterial infections. while bacteria commonly reproduce themselves outside of cells and have metabolic functions against which antibiotics can be directed, viruses replicate in the host c ... | 2007 | 17224068 |
| adjuvant-enhanced antibody responses to recombinant proteins correlates with protection of mice and monkeys to orthopoxvirus challenges. | recombinant proteins are being evaluated as smallpox and monkeypox vaccines because of their perceived safety compared to live vaccinia virus. previously, we demonstrated that three or more injections of a ribi-type adjuvant with a combination of three proteins from the outer membranes of intracellular (l1 protein) and extracellular (a33 and b5 proteins) forms of vaccinia virus protected mice against a lethal intranasal challenge with vaccinia virus. here, we compared several adjuvants and found ... | 2007 | 17229505 |
| use of atomic force microscopy as a diagnostic tool to identify orthopoxvirus. | atomic force microscopy (afm) is a versatile technique that permits the imaging of surfaces and generates topographical images from a variety of materials. due to the fact that afm requires minimum sample manipulation, it is a valuable tool for studying biological materials such as cells, dna, bacteria and viruses. the aim of the present study was to standardize the afm technique as a diagnostic tool for detection of naturally occurring orthopoxviruses. the samples analyzed were collected during ... | 2007 | 17239966 |
| orthopoxvirus pan-genomic dna assay. | a genome-spanning assay is described that enables laboratory confirmation of infections with orthopoxviruses (opvs), particularly vaccinia, monkeypox, and variola viruses, which can cause vesiculo-pustular rash illnesses in humans. the assay uses a series of polymerase chain reaction (pcr) amplicons that overlap to span the approximately 200kilobase pair linear dna genome of opvs. corresponding amplicons of different viral isolates can then be compared by matching their restriction fragment leng ... | 2007 | 17254642 |
| synthesis and antiviral activities of new acyclic and "double-headed" nucleoside analogues. | to develop an understanding of the structure-activity relationships for the inhibition of orthopoxviruses by nucleoside analogues, a variety of novel chemical entities were synthesized. these included a series of pyrimidine 5-hypermodified acyclic nucleoside analogues based upon recently discovered new leads, and some previously unknown "double-headed" or "abbreviated" nucleosides. none of the synthetic products possessed significant activity against two representative orthopoxviruses; namely, v ... | 2007 | 17270235 |
| understanding orthopoxvirus interference with host immune responses to inform novel vaccine design. | jenner's original vaccine used cowpox virus. cowpox virus and, subsequently, vaccinia virus, a closely related orthopoxvirus, provided the means to eradicate smallpox. this history and the unique properties of the virus suggest that vaccinia virus will continue to provide a useful vaccine platform. yet, surprisingly, it has become apparent that much of the virus genome encodes accessory proteins that interfere with host immune responses to infection. manipulation of these genes offers the potent ... | 2007 | 17280481 |
| a new inhibitor of apoptosis from vaccinia virus and eukaryotes. | a new apoptosis inhibitor is described from vaccinia virus, camelpox virus, and eukaryotic cells. the inhibitor is a hydrophobic, multiple transmembrane protein that is resident in the golgi and is named gaap (golgi anti-apoptotic protein). stable expression of both viral gaap (v-gaap) and human gaap (h-gaap), which is expressed in all human tissues tested, inhibited apoptosis induced by intrinsic and extrinsic apoptotic stimuli. conversely, knockout of h-gaap by sirna induced cell death by apop ... | 2007 | 17319741 |
| selective phosphorylation of antiviral drugs by vaccinia virus thymidine kinase. | the antiviral activity of a new series of thymidine analogs was determined against vaccinia virus (vv), cowpox virus (cv), herpes simplex virus, and varicella-zoster virus. several compounds were identified that had good activity against each of the viruses, including a set of novel 5-substituted deoxyuridine analogs. to investigate the possibility that these drugs might be phosphorylated preferentially by the viral thymidine kinase (tk) homologs, the antiviral activities of these compounds were ... | 2007 | 17325220 |
| real-time pcr to identify variola virus or other human pathogenic orthopox viruses. | variola virus (family poxviridae, genus orthopoxvirus) and the closely related cowpox, vaccinia, and monkeypox viruses can infect humans. efforts are mounting to replenish the smallpox vaccine stocks, optimize diagnostic methods for poxviruses, and develop new antivirals against smallpox, because it is feared that variola virus might be used as a weapon of bioterrorism. | 2007 | 17332145 |
| n-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6- ethenocycloprop[f]isoindol-2-(1h)-yl)carboxamides: identification of novel orthopoxvirus egress inhibitors. | a series of novel, potent orthopoxvirus egress inhibitors was identified during high-throughput screening of the viropharma small molecule collection. using structure--activity relationship information inferred from early hits, several compounds were synthesized, and compound 14 was identified as a potent, orally bioavailable first-in-class inhibitor of orthopoxvirus egress from infected cells. compound 14 has shown comparable efficaciousness in three murine orthopoxvirus models and has entered ... | 2007 | 17335190 |
| immunological memory after exposure to variola virus, monkeypox virus, and vaccinia virus. | we compared cellular and humoral immunity to vaccinia virus (vv) in individuals exposed to 3 different orthopoxviruses: 154 individuals previously vaccinated with vv, 7 individuals with a history of monkeypox virus infection, and 8 individuals with a history of variola virus infection. among individuals vaccinated >20 years prior, 9 (14%) of 66 individuals demonstrated vv-specific interferon (ifn)- gamma enzyme-linked immunospot (elispot) assay responses; 21 (50%) of 42 had lymphoproliferative ( ... | 2007 | 17357051 |
| generalized fatal cowpox virus infection in a cat with transmission to a human contact case. | a 4-month-old female domestic shorthair cat was infected by a virus of the poxvirus family. the animal developed a severe pneumonia and generalized ulcerating lesions of the skin. histologically, typical eosinophilic intracytoplasmic inclusion bodies indicative of an orthopoxvirus (opv) infection were present. the lung showed grey-white to haemorrhagic nodular lesions with a central zone of complete necrosis of alveolar and bronchial tissue. electron microscopy from skin and lung nodules reveale ... | 2007 | 17359444 |
| efficacy of the antipoxvirus compound st-246 for treatment of severe orthopoxvirus infection. | efficacy of the new antipoxvirus compound st-246 was evaluated as treatment of monkeypox (mpx) virus infection in a ground squirrel model of the disease. ground squirrels were given a lethal dose of mpx virus and were then treated orally at various times post-inoculation (pi) with 100 mg/kg/day of st-246. morbidity and mortality, clinical laboratory results, viral load, and pathology of placebo and treatment groups were compared. all animals that started treatment with st-246 on days 0, 1, 2, an ... | 2007 | 17426185 |
| serological survey of virus infection among wild house mice (mus domesticus) in the uk. | the serological prevalence of 13 murine viruses was surveyed among 103 wild-caught and 51 captive-bred house mice (mus domesticus), originating from several trapping locations in northwest england, using blood samples obtained during routine health screening of an established wild mouse colony. a high proportion of recently caught wild mice were seropositive for mouse hepatitis virus (86%), mouse cytomegalovirus (79%), mouse thymic virus (78%), mouse adenovirus (68%), mouse parvovirus (59%) and ... | 2007 | 17430622 |
| b5r gene based sequence analysis of indian buffalopox virus isolates in relation to other orthopoxviruses. | we determined complete nucleotide sequence of b5r gene homologue of vaccinia virus (vacv) in five buffalopox virus (bpxv) isolates of indian origin. the obtained sequences were compared with themselves and with corresponding sequences of the other orthopoxviruses. sequence analysis revealed 99.799.8% and 99.499.7% identities among the bpxv isolates for b5r gene at the nucleotide and amino acid levels, respectively. sequence identities of b5r gene between bpxv and vacv isolates (98.199.7%) or oth ... | 2007 | 17432943 |
| long-lasting stability of vaccinia virus (orthopoxvirus) in food and environmental samples. | poxviruses are known to remain infectious in the scabs of patients for months to years. the aim of this study was to investigate viral stability in storm water, food or gauze spiked with vaccinia virus strain munich 1 (vacv m1). storm water, storm water supplemented with either fetal calf serum (fcs) or potting soil was stored at two different temperatures (refrigerator, room temperature; 4 degrees c/25 degrees c). in addition, we analysed the viability of vacv m1 on the surface of bread, salad, ... | 2007 | 17456141 |
| dominance and diversity in the primary human cd4 t cell response to replication-competent vaccinia virus. | vaccination with replication-competent vaccinia protects against heterologous orthopoxvirus challenge. cd4 t cells have essential roles helping functionally important ab and cd8 antiviral responses, and contribute to the durability of vaccinia-specific memory. little is known about the specificity, diversity, or dominance hierarchy of orthopoxvirus-specific cd4 t cell responses. we interrogated vaccinia-reactive cd4 in vitro t cell lines with vaccinia protein fragments expressed from an unbiased ... | 2007 | 17475867 |
| camelpox virus encodes a schlafen-like protein that affects orthopoxvirus virulence. | camelpox virus (cmlv) gene 176r encodes a protein with sequence similarity to murine schlafen (m-slfn) proteins. in vivo, short and long members of the m-slfn family inhibited t-cell development, whereas in vitro, only short m-slfns caused arrest of fibroblast growth. cmlv 176 protein (v-slfn) is most closely related to short m-slfns; however, when expressed stably in mammalian cells, v-slfn did not inhibit cell growth. v-slfn is a predominantly cytoplasmic 57 kda protein that is expressed throu ... | 2007 | 17485525 |
| recombinant modified vaccinia virus ankara provides durable protection against disease caused by an immunodeficiency virus as well as long-term immunity to an orthopoxvirus in a non-human primate. | recombinant and non-recombinant modified vaccinia virus ankara (mva) strains are currently in clinical trials as human immunodeficiency virus-1 (hiv) and attenuated smallpox vaccines, respectively. here we tested the ability of a recombinant mva delivered by alternative needle-free routes (intramuscular, intradermal, or into the palatine tonsil) to protect against immunodeficiency and orthopoxvirus diseases in a non-human primate model. rhesus macaques were immunized twice 1 month apart with mva ... | 2007 | 17499326 |
| [biological microchip for identification of orthopoxviruses and agents causing the same clinical picture as in smallpox]. | a method based on hybridization of simultaneously amplified gene fragments of orthopoxviruses and herpesviruses with oligonucleotide probes immobilized on a microarray has been developed. the method permits identification of 6 orthopoxvirus species and three types of herpesviruses, including varicella zoster, within 6 hours. | 2007 | 17500239 |
| [rapid differential diagnosis of orthopoxviruses and herpesviruses based upon multiplex real-time pcr]. | variola virus, belonging to orthopoxviridae family, is one of the most dangerous human pathogens that could be used as biological weapon. we have developed a new rapid assay, based upon real-time pcr and melting temperatures analysis of amplicons, for the contemporary detection of orthopoxvirus, vzv and hsv1-2, that are the most important infectious agents to be considered for differential diagnosis. | 2007 | 17515675 |
| in vivo imaging of cidofovir treatment of cowpox virus infection. | variola virus and other members of the genus orthopoxviruses constitute a prominent bioterrorism and public health threat. treatment with the anti-viral drug cidofovir inhibits replication of orthopoxviruses in vitro and in vivo. in this study, we visualized the effect of cidofovir on viral kinetics in orthopoxvirus infected mice by using whole-body fluorescence imaging (fi). we engineered a cowpox virus (cpv) expressing the enhanced green fluorescent protein (gfp). single-step growth curves and ... | 2007 | 17524511 |
| zoonotic orthopoxviruses encode a high-affinity antagonist of nkg2d. | nk and t lymphocytes express both activating and inhibiting receptors for various members of the major histocompatibility complex class i superfamily (mhcisf). to evade immunologic cytotoxicity, many viruses interfere with the function of these receptors, generally by altering the displayed profile of mhcisf proteins on host cells. using a structurally constrained hidden markov model, we discovered an orthopoxvirus protein, itself distantly class i-like, that acts as a competitive antagonist of ... | 2007 | 17548517 |
| the first outbreak of camelpox in syria. | in this study we report the first outbreak of camelpox in two provinces in syria. clinical symptoms started with fever, salivation and general exanthema. the main features were facial and legs oedema, pustules on the mucosa of the lips and a high rate of abortion. lesions may also occur on the whole body including scrotum and udder. specimens were investigated by electron microscopy, virus isolation in cell culture and embryonated eggs and by immunohistochemistry. the causative agent was identif ... | 2007 | 17551230 |
| genomic sequence of a clonal isolate of the vaccinia virus lister strain employed for smallpox vaccination in france and its comparison to other orthopoxviruses. | since 1980 there has been global eradication of smallpox due to the success of the vaccination programme using vaccinia virus (vacv). during the eradication period, distinct vacv strains circulated, the lister strain being the most commonly employed in europe. analysis of the safety of smallpox vaccines has suggested that they display significant heterogeneity. to gain a more detailed understanding of the diversity of vacv strains it is important to determine their genomic sequences. although th ... | 2007 | 17554021 |
| antibody responses to vaccinia membrane proteins after smallpox vaccination. | vaccinia virus (vv) membrane proteins are candidates for orthopoxvirus subunit vaccines and potential targets for therapeutic antibodies. human antibody responses to these proteins after vv vaccination have not been well characterized. | 2007 | 17570109 |
| characterization of chimpanzee/human monoclonal antibodies to vaccinia virus a33 glycoprotein and its variola virus homolog in vitro and in a vaccinia virus mouse protection model. | three distinct chimpanzee fabs against the a33 envelope glycoprotein of vaccinia virus were isolated and converted into complete monoclonal antibodies (mabs) with human gamma 1 heavy-chain constant regions. the three mabs (6c, 12c, and 12f) displayed high binding affinities to a33 (k(d) of 0.14 nm to 20 nm) and may recognize the same epitope, which was determined to be conformational and located within amino acid residues 99 to 185 at the c terminus of a33. one or more of the mabs were shown to ... | 2007 | 17581986 |
| the identification and characterization of a monoclonal antibody to the vaccinia virus e3 protein. | monoclonal antibodies with reactivity to vaccinia virus specific proteins are useful reagents to study the proteins as well as to help understand aspects of the poxvirus life cycle. using a vaccinia virus proteomics microarray, we found a hybridoma (mab 3015b2) from a vaccinia virus vaccinated mouse that reacted with the product of the e3l gene. the specificity to the e3 protein was confirmed by western blotting and immunofluorescence of cells infected with either wild-type vaccinia virus or a m ... | 2007 | 17583368 |
| poxviruses as possible vectors for horizontal transfer of retroposons from reptiles to mammals. | poxviruses (poxviridae) are a family of double-stranded dna viruses with no rna stage. members of the genus orthopoxvirus (opv) are highly invasive and virulent. it was recently shown that the taterapox virus (tatv) from a west african rodent is the sister of camelpox virus and therefore belongs to the clade closest to the variola virus (varv), the etiological agent of smallpox. although these opvs are among the most dreaded pathogens on earth, our current knowledge of their genomes, their origi ... | 2007 | 17623783 |
| characterization of uvc light sensitivity of vaccinia virus. | interest in airborne smallpox transmission has been renewed because of concerns regarding the potential use of smallpox virus as a biothreat agent. air disinfection via upper-room 254-nm germicidal uv (uvc) light in public buildings may reduce the impact of primary agent releases, prevent secondary airborne transmission, and be effective prior to the time when public health authorities are aware of a smallpox outbreak. we characterized the susceptibility of vaccinia virus aerosols, as a surrogat ... | 2007 | 17644645 |
| an ectromelia virus profilin homolog interacts with cellular tropomyosin and viral a-type inclusion protein. | profilins are critical to cytoskeletal dynamics in eukaryotes; however, little is known about their viral counterparts. in this study, a poxviral profilin homolog, ectromelia virus strain moscow gene 141 (ectv-ph), was investigated by a variety of experimental and bioinformatics techniques to characterize its interactions with cellular and viral proteins. | 2007 | 17650322 |
| efficacy of n-methanocarbathymidine in treating mice infected intranasally with the ihd and wr strains of vaccinia virus. | n-methanocarbathymidine [(n)-mct] is a newly identified inhibitor of orthopoxvirus replication in cell culture and in mice. limited published animal studies indicated the compound is effective by intraperitoneal (i.p.) route at 10-100 mg/(kg day). more extensive studies using different treatment regimens in intranasally infected mice were conducted in order to further explore the potential of this compound compared to cidofovir in treating vaccinia virus infections. (n)-mct was given twice a day ... | 2007 | 17658623 |
| brazilian vaccinia virus strains show genetic polymorphism at the ati gene. | nucleotide sequence comparison of the internal region of the ati gene of members of the orthopoxvirus genera revealed that this gene is variable among different species, although within members of the same species it is considered to be well conserved. previous studies indicated that there is genetic variability in the ati gene among some brazilian vaccinia virus strains. to further investigate this variability, we performed molecular analysis of the internal region of the ati gene of eight braz ... | 2007 | 17671837 |
| buffalopox: an emerging and re-emerging zoonosis. | outbreaks of buffalopox or pox-like infections affecting buffaloes, cows and humans have been recorded in many parts of the world. since the first outbreak in india, a large number of epidemics have occurred. unlike in the previous years, generalized forms of the disease are now rare; however, there are severe local forms of the disease affecting the udder and teats, leading to mastitis thereby undermining the productivity of milk animals. the causative agent buffalopox virus (bpxv) is a member ... | 2007 | 17692147 |
| lsm proteins bind and stabilize rnas containing 5' poly(a) tracts. | many orthopoxvirus messenger rnas have an unusual nontemplated poly(a) tract of 5 to 40 residues at the 5' end. the precise function of this feature is unknown. here we show that 5' poly(a) tracts are able to repress rna decay by inhibiting 3'-to-5' exonucleases as well as decapping of rna substrates. uv cross-linking analysis demonstrated that the lsm complex associates with the 5' poly(a) tract. furthermore, recombinant lsm1-7 complex specifically binds 5' poly(a) tracts 10 to 21 nucleotides i ... | 2007 | 17694069 |
| monkeypox-induced immunity and failure of childhood smallpox vaccination to provide complete protection. | following the u.s. monkeypox outbreak of 2003, blood specimens and clinical and epidemiologic data were collected from cases, defined by standard definition, and household contacts of cases to evaluate the role of preexisting (smallpox vaccine-derived) and acquired immunity in susceptibility to monkeypox disease and clinical outcomes. orthopoxvirus-specific immunoglobulin g (igg), igm, cd4, cd8, and b-cell responses were measured at approximately 7 to 14 weeks and 1 year postexposure. associatio ... | 2007 | 17715329 |
| synergistic efficacy of the combination of st-246 with cmx001 against orthopoxviruses. | the combination of st-246 and hexadecyloxypropyl-cidofovir or cmx001 was evaluated for synergistic activity in vitro against vaccinia virus and cowpox virus (cv) and in vivo against cv. in cell culture the combination was highly synergistic against both viruses, and the results suggested that combined treatment with these agents might offer superior efficacy in vivo. for animal models, st-246 was administered orally with or without cmx001 to mice lethally infected with cv. treatments began 1, 3, ... | 2007 | 17724153 |
| viremia in human cowpox virus infection. | several poxviruses can infect humans and cause diseases of varying severity. besides the eradicated variola virus that induced high mortality rates, numerous further human pathogenic orthopoxviruses are potentially fatal but generally cause less severe infections. while infection-related viremia was described for variola virus and seems to be rare for monkeypox virus, it is still debated for vaccinia virus. so far, viremia in cowpox virus-infected humans has not been reported. | 2007 | 17765007 |
| effect of oral treatment with hexadecyloxypropyl-[(s)-9-(3-hydroxy-2- phosphonylmethoxypropyl)adenine] [(s)-hpmpa] or octadecyloxyethyl-(s)-hpmpa on cowpox or vaccinia virus infections in mice. | we have previously reported that (s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, or (s)-hpmpa, is active in vitro against cowpox virus (cv) and vaccinia virus (vv) but is not active orally in animals. however, the ether lipid esters of (s)-hpmpa, hexadecyloxypropyl-[(s)-hpmpa] [hdp-(s)-hpmpa] and octadecyloxyethyl-[(s)-hpmpa] [ode-(s)-hpmpa], had significantly enhanced activity in vitro and are orally bioavailable in mice. in the current study, hdp-(s)-hpmpa and ode-(s)-hpmpa were prepared i ... | 2007 | 17846137 |
| poxviruses and the passive quest for novel hosts. | poxviruses are famous, or infamous, as agents of disease introduced into novel host species and between populations of the same species. this discussion concerns selected examples of poxviruses associated with vertebrate infections, i.e., the chordopoxvirus subfamily of the family poxviridae. brief note is made of examples of members of the genera leporipoxvirus and parapoxvirus-like agents that have been recognized to have significant trans-host species impact. the remaining bulk of the discuss ... | 2007 | 17848071 |
| inactivation of orthopoxvirus for diagnostic pcr analysis. | diagnoses of ongoing viral infections commonly rely on pcr methodology. sample material that may contain hazardous virus should be efficiently inactivated in biological containment or bed-side before diagnostic pcr analysis. surprisingly little documentation is available for inactivation of human viral pathogens by inactivation reagents that allow for subsequent pcr diagnostics. it is now shown that pathogenic dna viruses (orthopoxvirus) are completely inactivated by a commercially available roc ... | 2007 | 17850891 |
| activities of several classes of acyclic nucleoside phosphonates against camelpox virus replication in different cell culture models. | camelpox virus (cmlv) is the closest known virus to variola virus. here we report on the anti-cmlv activities of several acyclic nucleoside phosphonates (anps) related to cidofovir [(s)-1-(3-hydroxy-2-phosphonomethoxypropyl)cytosine (hpmpc; vistide)] against two cmlv strains, cml1 and cml14. cytopathic effect (cpe) reduction assays performed with human embryonic lung fibroblast monolayers revealed the selectivities of the first two classes of anps (chpmpa, hpmpdap, and hpmpo-dapy) and of the hex ... | 2007 | 17893157 |
| "recreational" drug abuse associated with failure to mount a proper antibody response after a generalised orthopoxvirus infection. | infections with orthopoxviruses usually lead to cross-protection among all species of the family. this has been a prerequisite for successful eradication of smallpox. here we report the rare case of a 17-year-old male, who survived a generalised cowpox virus infection of unusual severity but surprisingly did not show a proper seroconversion. only a very weak antibody production was observed in early and late serum samples, which initially appeared to be cowpox virus specific in immunofluorescenc ... | 2007 | 17917699 |
| yaba monkey tumor virus encodes a functional inhibitor of interleukin-18. | interleukin-18 (il-18) is a critical proinflammatory cytokine whose extracellular bioactivity is regulated by a cellular il-18 binding protein (il-18bp). many poxviruses have acquired variants of this il-18bp gene, some of which have been shown to act as viral virulence factors. yaba monkey tumor virus (ymtv) encodes a related family member, 14l, which is similar to the orthopoxvirus il-18bps. ymtv 14l was expressed from a baculovirus system and tested for its ability to bind and inhibit il-18. ... | 2008 | 17959666 |
| orthopoxvirus detection in environmental specimens during suspected bioterror attacks: inhibitory influences of common household products. | after terrorists attacked the united states in 2001, the appearance of letters and other objects containing powdery substances with unknown potentials for biological threat focused attention on the speed, sensitivity, and reliability of diagnostic methods. this study summarizes the abilities and limitations of real-time pcr, electron microscopy (em), and virus isolation when used to detect potential bioweapons. in particular, we investigated the inhibitory influences of different common househol ... | 2008 | 17965204 |
| cowpox virus exploits the endoplasmic reticulum retention pathway to inhibit mhc class i transport to the cell surface. | major histocompatibility complex (mhc) class i molecules assemble with peptides in the er lumen and are transported via golgi to the plasma membrane for recognition by t cells. inhibiting mhc assembly, transport, and surface expression are common viral strategies of evading immune recognition. cowpox virus, a clinically relevant orthopoxvirus, downregulates mhc class i expression on infected cells. however, the viral protein(s) and mechanisms responsible are unknown. we identify cpxv203 as a cow ... | 2007 | 18005752 |
| genomic sequence of chorioallantois vaccinia virus ankara, the ancestor of modified vaccinia virus ankara. | chorioallantois vaccinia virus ankara (cva) is the parental virus of modified vaccinia virus ankara (mva), which was derived from cva by more than 570 passages in chicken embryo fibroblasts (cef). mva became severely host-cell-restricted to avian cells and has strongly diminished virulence in mammalian hosts, while maintaining good immunogenicity. we determined the complete coding sequence of the parental cva and mapped the exact positions of the six major deletions that emerged in the mva genom ... | 2007 | 18024893 |
| prevalence of antibodies against orthopoxviruses among residents of likouala region, republic of congo: evidence for monkeypox virus exposure. | monkeypox virus is a zoonotic orthopoxvirus (opx) of west and central sub-saharan africa. we conducted a cross-sectional serosurvey in likouala region, republic of congo to assess exposure to opx. whole blood was collected using nobuto blood filter strips (nbfs). titers of igm and igg to opx were assessed using an enzyme-linked immunosorbent assay. demographic and clinical characteristics were compared with serostatus using the chi-square test or fisher's exact test. multivariate logistic regres ... | 2007 | 18165539 |
| vaccination of balb/c mice with escherichia coli-expressed vaccinia virus proteins a27l, b5r, and d8l protects mice from lethal vaccinia virus challenge. | the potential threat of smallpox use in a bioterrorist attack has heightened the need to develop an effective smallpox vaccine for immunization of the general public. vaccination with the current smallpox vaccine, dryvax, produces protective immunity but may result in adverse reactions for some vaccinees. a subunit vaccine composed of protective vaccinia virus proteins should avoid the complications arising from live-virus vaccination and thus provide a safer alternative smallpox vaccine. in thi ... | 2008 | 18199639 |
| cowpox infection transmitted from a domestic cat. | a 21-year-old immunocompetent woman developed a cowpox infec-tion,while working as a veterinarian's assistant in a rural area. she had never received vaccinia immunization and came in contact with a fatally-infected house cat. under symptomatic treatment, the infection remained localized to one cheek and cleared over 3 weeks with substantial dermal-subcutaneous tissue destruction. orthopoxvirus detection by pcr is a modern diagnostic standard, in addition to identification by negative-contrast e ... | 2008 | 18201221 |
| comparative proteomics of human monkeypox and vaccinia intracellular mature and extracellular enveloped virions. | orthopoxviruses are among the largest and most complex of the animal viruses. in response to the recent emergence of monkeypox in africa and the threat of smallpox bioterrorism, two orthopoxviruses with different pathogenic potentials, human monkeypox virus and vaccinia virus, were proteomically compared with the goal of identifying proteins required for pathogenesis. orthopoxviruses were grown in hela cells to two different viral forms (intracellular mature virus and extracellular enveloped vir ... | 2008 | 18205298 |
| brazilian vaccinia viruses and their origins. | although the world health organization (who) declared global smallpox eradicated in 1980, concerns over emergent poxvirus infections have increased. most poxvirus infections are zoonotic; exploring their genetic diversity will illuminate the genetic and evolutionary aspects of poxvirus infections, ecology, and epidemiology. in recent decades, several strains of the orthopoxvirus vaccinia virus (vacv) have been isolated throughout brazil, including genetically distinct isolates within the same ou ... | 2007 | 18214166 |
| poxvirus cancer therapy. | despite many advances in chemotherapy and other medical techniques, patients with cancer often develop local recurrence or metastatic spread. recent advances in molecular biology and tumor immunology have led to the design of many new anti-tumor vaccines. such approaches are now using recombinant viruses to treat different types of cancer. from these new developments, innovative fields are emerging: vaccine virotherapy, viral immunotherapy, oncolytic virotherapy and drug virotherapy. many viruse ... | 2006 | 18221156 |
| activity of the anti-orthopoxvirus compound st-246 against vaccinia, cowpox and camelpox viruses in cell monolayers and organotypic raft cultures. | the potential use of variola virus as a biological weapon has renewed efforts in the development of antiviral agents against orthopoxviruses. st-246 [4-trifluoromethyl-n-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-di oxo-4,6-ethenocycloprop [f]isoindol-2(1 h)-yl)-benzamide] is an anti-orthopoxvirus compound active against several orthopoxviruses including vaccinia virus (vv), cowpox virus (cpv), camelpox virus (cmlv), ectromelia virus (ectv) and variola virus in cell culture. the compound has been shown ... | 2007 | 18240860 |
| kinetic analysis of a complete poxvirus transcriptome reveals an immediate-early class of genes. | vaccinia virus is the prototypic orthopoxvirus and was the vaccine used to eradicate smallpox, yet the expression profiles of many of its genes remain unknown. using a genome tiling array approach, we simultaneously measured the expression levels of all 223 annotated vaccinia virus genes during infection and determined their kinetics. for 95% of these genes, significant transcript levels were detected. most remarkably, classification of the genes by their expression profiles revealed 35 genes ex ... | 2008 | 18245380 |
| spectrum of infection and risk factors for human monkeypox, united states, 2003. | for the 2003 monkeypox virus (mpxv) outbreak in the united states, interhuman transmission was not documented and all case-patients were near or handled mpxv-infected prairie dogs. we initiated a case-control study to evaluate risk factors for animal-to-human mpxv transmission. participants completed a questionnaire requesting exposure, clinical, and demographic information. serum samples were obtained for analysis of immunoglobulin g (igg) and igm to orthopoxvirus. when data were adjusted for s ... | 2007 | 18252104 |
| structure and mechanism of ifn-gamma antagonism by an orthopoxvirus ifn-gamma-binding protein. | ectromelia virus (ectv) encodes an ifn-gamma-binding protein (ifn-gammabp(ectv)) that disrupts ifn-gamma signaling and its ability to induce an antiviral state within cells. ifn-gammabp(ectv) is an important virulence factor that is highly conserved (>90%) in all orthopoxviruses, including variola virus, the causative agent of smallpox. the 2.2-a crystal structure of the ifn-gammabp(ectv)/ifn-gamma complex reveals ifn-gammabp(ectv) consists of an ifn-gammar1 ligand-binding domain and a 57-aa hel ... | 2008 | 18252829 |
| a role for nkg2d in nk cell-mediated resistance to poxvirus disease. | ectromelia virus (ectv) is an orthopoxvirus (opv) that causes mousepox, the murine equivalent of human smallpox. c57bl/6 (b6) mice are naturally resistant to mousepox due to the concerted action of innate and adaptive immune responses. previous studies have shown that natural killer (nk) cells are a component of innate immunity that is essential for the b6 mice resistance to mousepox. however, the mechanism of nk cell-mediated resistance to opv disease remains undefined. here we show that b6 mic ... | 2008 | 18266471 |
| smallpox virus resequencing genechips can also rapidly ascertain species status for some zoonotic non-variola orthopoxviruses. | we recently developed a set of seven resequencing genechips for the rapid sequencing of variola virus strains in the who repository of the centers for disease control and prevention. in this study, we attempted to hybridize these genechips with some known non-variola orthopoxvirus isolates, including monkeypox, cowpox, and vaccinia viruses, for rapid detection. | 2008 | 18272713 |
| single-dose safety and pharmacokinetics of st-246, a novel orthopoxvirus egress inhibitor. | st-246 is a novel, potent orthopoxvirus egress inhibitor that is being developed to treat pathogenic orthopoxvirus infections of humans. this phase i, double-blind, randomized, placebo-controlled single ascending dose study (first time with humans) was conducted to determine the safety, tolerability, and pharmacokinetics of st-246 in healthy human volunteers. st-246 was administered in single oral doses of 500, 1,000, and 2,000 mg to fasting healthy volunteers and 1,000 mg to nonfasting healthy ... | 2008 | 18316519 |
| the highly conserved orthopoxvirus 68k ankyrin-like protein is part of a cellular scf ubiquitin ligase complex. | the 68k ankyrin-like protein (68k-ank) of unknown function is highly conserved among orthopoxviruses and contains ankyrin repeats and an f-box-like domain. we performed a yeast-two-hybrid screen with 68k-ank to find interacting proteins. from a human and a murine cdna library, 99% of the interaction partners were s-phase kinase-associated protein 1a (skp1a), a part of the scf ubiquitin ligase complex. 68k-ank co-immunoprecipitated with components of the endogenous, mammalian scf ubiquitin ligase ... | 2008 | 18353424 |
| a simple restriction fragment pcr approach for discrimination of humanpathogenic old world animal orthopoxvirus species. | there are reliable polymerase chain reaction assays available for exclusion of variola virus from other poxviruses. however, the discrimination of humanpathogenic animal orthopoxviridae is more challenging because of the high genomic conservation. based on the variability of the a36r gene, we describe a simple 20 min pcr assay followed by a 1 h digest with 3 different restriction enzymes. this assay enables rapid discrimination between cowpox virus and monkeypox virus and discrimination of the m ... | 2008 | 18388986 |
| the orthopoxvirus type i ifn binding protein is essential for virulence and an effective target for vaccination. | nonliving antiviral vaccines traditionally target proteins expressed at the surface of the virion with the hope of inducing neutralizing antibodies. orthopoxviruses (opvs), such as the human smallpox virus and the mouse-equivalent ectromelia virus (ectv; an agent of mousepox), encode immune response modifiers (irms) that can increase virulence by decreasing the host immune response. we show that one of these irms, the type i interferon (ifn) binding protein (bp) of ectv, is essential for ectv vi ... | 2008 | 18391063 |
| retrospective analysis of monkeypox infection. | serologic cross-reactivity between orthopoxviruses is a substantial barrier to laboratory diagnosis of specific orthopoxvirus infections and epidemiologic characterization of disease outbreaks. historically, time-consuming and labor-intensive strategies such as cross-adsorbed neutralization assays, immunofluorescence assays, and hemagglutination-inhibition assays have been used to identify orthopoxvirus infections. we used cross-adsorption to develop a simple and quantitative postadsorption elis ... | 2008 | 18394277 |
| [human monkeypox]. | unlike other recent viral emergences, which were in majority caused by rna viruses, the monkeypox results from infection by a dna virus, an orthopoxvirus closely related to both vaccine and smallpox viruses and whose two genomic variants are known. unexpectedly isolated from captive asiatic monkeys and first considered as an laboratory curiosity, this virus was recognised in 1970 as an human pathogen in tropical africa. here it was responsible for sporadic cases following intrusions (for hunting ... | 2009 | 18394820 |
| laboratory-acquired vaccinia exposures and infections--united states, 2005-2007. | the last case of naturally acquired smallpox disease, caused by the orthopoxvirus variola virus (varv), occurred in 1977, and the last laboratory-acquired case occurred in 1978. smallpox was eradicated largely as the result of a worldwide vaccination campaign that used the related orthopoxvirus, vaccinia virus (vacv), as a live virus vaccine. routine childhood vaccination for smallpox in the united states was terminated by 1972, but vaccination continues or has been reintroduced for specific gro ... | 2008 | 18418346 |
| severe eczema vaccinatum in a household contact of a smallpox vaccinee. | we report the first confirmed case of eczema vaccinatum in the united states related to smallpox vaccination since routine vaccination was discontinued in 1972. a 28-month-old child with refractory atopic dermatitis developed eczema vaccinatum after exposure to his father, a member of the us military who had recently received smallpox vaccine. the father had a history of inactive eczema but reportedly reacted normally to the vaccine. the child's mother also developed contact vaccinia infection. | 2008 | 18419490 |
| differential antigen requirements for protection against systemic and intranasal vaccinia virus challenges in mice. | the development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding protective antigens and the requirement for multiple boost immunizations to afford protective immunity. here we explore the protective efficacy of replication-incompetent, recombinant adenovirus serotyp ... | 2008 | 18448519 |
| evaluation of orally delivered st-246 as postexposure prophylactic and antiviral therapeutic in an aerosolized rabbitpox rabbit model. | orthopoxviruses, such as variola and monkeypox viruses, can cause severe disease in humans when delivered by the aerosol route, and thus represent significant threats to both military and civilian populations. currently, there are no antiviral therapies approved by the u.s. food and drug administration (fda) to treat smallpox or monkeypox infection. in this study, we showed that administration of the antiviral compound st-246 to rabbits by oral gavage, once daily for 14 days beginning 1h postexp ... | 2008 | 18479761 |