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cytoplasmic interactions between decay-accelerating factor and intercellular adhesion molecule-1 are not required for coxsackievirus a21 cell infection.coxsackievirus a21 (cav-21) employs a cell receptor complex of decay-accelerating factor (daf) and intercellular adhesion molecule-1 (icam-1) for cell infectivity. in this study, the nature of potential extra- and/or intracellular interactions between daf and icam-1 involved in picornaviral cell entry was investigated. firstly, it was shown that intracellular interplay between daf and icam-1 is not required for cav-21 infection, as cav-21 lytic infection mediated via the daf/icam-1 receptor comp ...200010725413
short consensus repeat domain 1 of decay-accelerating factor is required for enterovirus 70 binding.enterovirus 70 (ev70), like several other human enteroviruses, can utilize decay-accelerating factor (daf [cd55]) as an attachment protein. using chimeric molecules composed of different combinations of the short consensus repeat domains (scrs) of daf and membrane cofactor protein (cd46), we show that sequences in scr1 of daf are essential for ev70 binding. of the human enteroviruses that can bind to daf, only ev70 and coxsackievirus a21 require sequences in scr1 for this interaction.19989765493
demonstration of the specificity of poliovirus encapsidation using a novel replicon which encodes enzymatically active firefly luciferase.the specificity of poliovirus encapsidation has been studied using a novel chimeric genome in which the gene encoding firefly luciferase has been substituted for the vp2-vp3-vp1 genes of the poliovirus capsid (p1) gene. transfection of rna transcribed in vitro from this genome resulted in a vp4-luciferase fusion protein which retained luciferase enzyme activity. since the detection of enzyme activity was dependent upon replication of the transfected rna genome, we refer to these genomes as repli ...19989527910
enterovirus capsid interactions with decay-accelerating factor mediate lytic cell infection.the cellular receptor usage of numerous human enteroviruses can differ significantly between low-cell-culture-passaged clinical isolates and highly laboratory-passaged prototype strains. the prototype strain of coxsackievirus a21 (cva21) displays a dual-receptor specificity as determined with a receptor complex consisting of decay-accelerating factor (daf) and intercellular adhesion molecule 1 (icam-1). in this study, the cellular receptor interactions of low-cell-passage cva21 clinical isolates ...200414722298
binding to decay-accelerating factor is not required for infection of human leukocyte cell lines by enterovirus 70.enterovirus 70 (ev70) is one of several human enteroviruses that exhibit a propensity for infecting the central nervous system (cns). the mechanisms by which neurotropic enteroviruses gain access to and invade the cns are poorly understood. one possibility is that circulating leukocytes become infected and carry neurotropic enteroviruses to the cns. we examined the ability of ev70 to infect cell lines derived from lymphoid, myeloid, and monocytic lineages. most leukocyte cell lines tested bound ...200414990687
a decay-accelerating factor-binding strain of coxsackievirus b3 requires the coxsackievirus-adenovirus receptor protein to mediate lytic infection of rhabdomyosarcoma cells.the composition of the cellular receptor complex for coxsackievirus b3 (cvb3) has been an area of much contention for the last 30 years. recently, two individual components of a putative cvb3 cellular receptor complex have been identified as (i) decay-accelerating factor (daf) and (ii) the coxsackievirus-adenovirus receptor protein (car). the present study elucidates the individual roles of daf and car in cell entry of cvb3 nancy. first, we confirm that the daf-binding phenotype of cvb3 correlat ...19979371658
internalization of human rhinovirus 14 into hela and icam-1-transfected bhk cells.virus adsorption and uptake of human rhinovirus 14 (hrv14) were studied with hela cells and baby hamster kidney (bhk) cells which were transfected with the hrv14 receptor intercellular adhesion molecule-1 (icam-1). transmission electron microscopy of hela cells revealed that hrv14 was internalized via clathrin-coated pits and -coated vesicles. a minority of virus particles also used uncoated vesicles for entry. the internalization showed the characteristics of receptor-mediated endocytosis. pres ...19979255760
mouse cells expressing human intercellular adhesion molecule-1 are susceptible to infection by coxsackievirus a21.competitive viral binding assays have revealed previously that coxsackievirus a21 (cav21) and human rhinovirus 14 (hrv14) share a common cell surface receptor. more recently, intercellular adhesion molecule-1 (icam-1) has been identified as the cellular receptor for hrv-14. also, anti-icam-1 monoclonal antibodies (mabs) blocked infection by hrv14, cav13, cav18, and cav21, suggesting that these viruses share this receptor; however, this has never been established by more direct methods. in this s ...19978985417
novel role for decay-accelerating factor in coxsackievirus a21-mediated cell infectivity.decay-accelerating factor (daf) is involved in the cell membrane attachment of many human enteroviruses. presently, further specific active roles of daf in mediating productive cell infection and in the pathogenesis of natural enterovirus infection are poorly understood. in an attempt to more fully understand the role of daf in lytic cell infection we examined the specific interactions of the prototype strain of coxsackievirus a21 (cva21) with surface-expressed daf. investigations into discrete ...200415507656
coxsackievirus a21 binds to decay-accelerating factor but requires intercellular adhesion molecule 1 for cell entry.it is becoming increasingly apparent that many viruses employ multiple receptor molecules in their cell entry mechanisms. the human enterovirus coxsackievirus a21 (cav21) has been reported to bind to the n-terminal domain of intercellular adhesion molecule 1 (icam-1) and undergo limited replication in icam-1-expressing murine l cells. in this study, we show that in addition to binding to icam-1, cav21 binds to the first short consensus repeat (scr) of decay-accelerating factor (daf). dual antibo ...19979151867
antibody binding to individual short consensus repeats of decay-accelerating factor enhances enterovirus cell attachment and infectivity.decay-accelerating factor (daf), a widely expressed membrane complement-regulatory protein, is utilized as a cellular receptor by many human enteric pathogens. we show here that the binding of two enteroviruses to individual short consensus repeats (scr) of daf on the cell surface is greatly augmented by mab binding to an alternate scr: coxsackievirus a21 binding to the scr1 of daf is increased by ab binding to scr3 and, conversely, echovirus 7 binding to scr3 is enhanced severalfold by ab bindi ...19989498772
clinical activity of pleconaril in an experimentally induced coxsackievirus a21 respiratory infection.a randomized, double-blind study assessed the efficacy and safety of pleconaril, a novel antiviral drug with broad-spectrum activity against picornaviruses, in the treatment of 33 adults with an experimentally induced viral respiratory infection. subjects received either pleconaril 200 mg twice daily (initial dose of 400 mg) or placebo for 7 days. fourteen hours after receiving the initial dose of either pleconaril or placebo, subjects were inoculated intranasally with 100 plaque-forming units o ...200010608746
antiviral activity and mechanism of action of 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (mdl-860).a nitrobenzene derivative, mdl-860, was found to inhibit plaque formation, cytopathic effect, or both in 11 of 12 picornaviruses at concentrations which did not affect cell growth. the compound did not directly inactivate the virus. mdl-860 inhibited actinomycin d-resistant [3h]uridine uptake in cells infected with coxsackievirus a21 or rhinovirus 1-a, whereas incorporation into uninfected cells was not inhibited. with three picornaviruses (echovirus type 12, poliovirus type 2, and rhinovirus ty ...19827181474
experiments on the spread of colds. ii. studies in volunteers with coxsackievirus a21. 19655318065
a survey of antibodies to adenovirus 8 and coxsackievirus a21 in human sera.studies have recently been published of surveys of antibodies to common respiratory viruses in human sera from several parts of the world. the present article reports the findings of a survey of antibodies to two more viruses (adenovirus type 8 and coxsackievirus type a21) in human sera mainly collected from six widely separated geographical regions (alaska, england, marshall islands, sarawak, south-west africa and tunisia).a world-wide geographical distribution of infection with these two virus ...19665296130
studies of respiratory viruses in personnel at an antarctic base.thirteen men wintering on an antarctic base were isolated from other human contact for 10 months. during this period coxsackievirus a21 and later influenza a2 virus were administered to some of the men. serum samples were collected from each of the men at monthly intervals.coxsackievirus a21 produced symptoms and apparently spread to uninoculated men. it also appears that repeated re-infections occurred and that the virus persisted in this small community for most of the period of isolation. hi ...19715282923
antipicornavirus activity of some diaryl methanes and aralkylaminopyridines.sixteen diarylmethanes and ten aralkylaminopyridines were initially evaluated for their in vitro activity against rhinoviruses 1a, 2 and 64 and against coxsackievirus a21 and for their oral prophylactic and therapeutic activity in mice challenged with coxsackievirus a21. based on these preliminary studies the diarylmethane (3,4-dichlorophenoxy)-(5 methylsulfonyl-2-pyridinyl)-methane and the aralkylaminopyridine (2-(3,4-dichlorobenzylamino)-5-methylsulfonylpyridine were compared with their oxygen ...19873034149
the complete nucleotide sequence of coxsackievirus a21.we have determined the complete nucleotide sequence of coxsackievirus a21 (cav-21), the first member of this enterovirus subgroup to be analysed in molecular detail. the sequence, which is 7401 nucleotides long, encodes an open reading frame of 2206 codons, preceded by a 5' non-coding region of 711 nucleotides and followed by a 3' non-coding region of 72 nucleotides plus a poly(a) tract. the most striking feature is the remarkable homology to the poliovirus (greater than 90% at the amino acid le ...19892584950
detection of enteroviruses using cdna and synthetic oligonucleotide probes.this study compares the detection of enterovirus rna by cdna probes prepared from both the 5' and 3' end of the genome of coxsackie a21 and b4 with the use of synthetic oligonucleotides prepared from short but highly conserved sequences in the 5' end non-coding region of the picornavirus genome. the cdna probes detected enteroviruses with a variable level of sensitivity which presumably depended on the degree of genomic homology with the detecting probes. generally probes from coxsackievirus a21 ...19892550504
antipicornavirus activity of substituted phenoxybenzenes and phenoxypyridines.phenoxybenzenes and phenoxypyridines were prepared and tested for the effect of substituents on antipicornavirus activity. the most active compound, 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile (8), demonstrated broad-spectrum antipicornavirus activity. compound 8 and several analogues each given orally prior to and during infection protected mice against an otherwise lethal challenge with coxsackievirus a21.19863005578
the nucleotide sequence of 3c proteinase region of the coxsackievirus a24 variant: comparison of the isolates in taiwan in 1985-1988.acute hemorrhagic conjunctivitis caused by coxsackievirus a24 variant (ca24v) first appeared in taiwan in october 1985, followed by two other sequential epidemics in 1986 and 1988. in order to know the evolutionary relationship of the ca24v strains isolated in taiwan, we first determined the nucleotide sequence of the 3c proteinase (3cpro) region of the prototype strain (eh24/70), isolated in singapore in 1970, by molecular cloning. the nucleotide sequence of the 3cpro region thus sequenced show ...19911647565
monoclonal antibody that inhibits infection of hela and rhabdomyosarcoma cells by selected enteroviruses through receptor blockade.balb/c mice were immunized with hela cells, and their spleen cells were fused with myeloma cells to produce hybridomas. initial screening of culture fluids from 800 fusion products in a cell protection assay against coxsackievirus b3 (cb3) and the cb3-rd virus variant yielded five presumptive monoclonal antibodies with three specificities: protection against cb3 on hela, protection against cb3-rd on rhabdomyosarcoma (rd) cells, and protection against both viruses on the respective cells. only on ...19863003376
antigenic conservation and divergence between the viral-specific proteins of poliovirus type 1 and various picornaviruses.immuneprecipitation analyses of various picornavirus-infected cell lysates were performed using antisera to poliovirus type 1-specific structural and nonstructural proteins. the results showed differing patterns of antigenic conservation and divergence. however, the vp3 and 2c polypeptides were strongly antigenically conserved among the large majority of these viruses. this conservation was especially notable given the degree of divergence exhibited by the other viral proteins and may be due to ...19852981447
interaction of coxsackievirus a21 with its cellular receptor, icam-1.coxsackievirus a21 (cav21), like human rhinoviruses (hrvs), is a causative agent of the common cold. it uses the same cellular receptor, intercellular adhesion molecule 1 (icam-1), as does the major group of hrvs; unlike hrvs, however, it is stable at acid ph. the cryoelectron microscopy (cryoem) image reconstruction of cav21 is consistent with the highly homologous crystal structure of poliovirus 1; like other enteroviruses and hrvs, cav21 has a canyon-like depression around each of the 12 five ...200111160747
nucleic acid sequence relationships between enterovirus serotypes.forty-eight different enterovirus serotypes were analysed by a nucleic-acid hybridization test using probes derived from the 3' end of coxsackievirus a21 (ca21) and b3 (cb3), poliovirus 3 (p3) and enterovirus 70 (e70). more than 90% of the serotypes could be detected with this collection of reagents. the cb3 probe reacted with all the coxsackie b viruses, with all three poliovirus serotypes, and with almost all of the 30 echo virus types tested. in addition some of the coxsackie a viruses and th ...19872456458
the complete nucleotide sequence of a variant of coxsackievirus a24, an agent causing acute hemorrhagic conjunctivitis.the complete nucleotide sequence was determined for the cdnas that represent the rna genome of the standard strain of a variant of coxsackievirus a24, the eh24/70, one of the agents causing acute hemorrhagic conjunctivitis. the genome is 7461 nucleotide long and is polyadenylated at the 3'-end terminus. following a 750-nucleotide 5'-noncoding region, there was a long open reading frame of 6642 nucleotides, which serve to encode a viral polyprotein consisting of 2214 amino acids. comparison of th ...19921317075
the importance of picornavirus infections in respiratory disease of man and other mammals.picornaviruses may be divided, by physicochemical properties, into enteroviruses, cardioviruses, caliciviruses, rhinoviruses and foot-and-mouth diseases viruses. although the respiratory tract may be the primary site of entry and multiplication for enteroviruses, cardioviruses and fmd viruses, few agents in these groups cause respiratory disease. a notable exception is coxsackievirus a21 which is an important cause of upper respiratory tract diseases in military recruits. the picornaviruses whic ...1975165133
encapsidation studies of poliovirus subgenomic replicons.the inclusion of a foreign marker gene, chloramphenicol acetyltransferase (cat) gene, into the poliovirus genome allows its replication and encapsidation to be easily monitored using a simple enzyme assay. such poliovirus replicons require the presence of helper virus for their successful propagation and thus are similar to defective interfering (di) viruses. in genomes containing the cat gene, the majority of the p1 virus capsid region of the poliovirus genome could be removed without destroyin ...19989680136
cellular receptor interactions of c-cluster human group a coxsackieviruses.the cellular receptor complex of coxsackievirus a21 (cva21), a c-cluster human enterovirus, is formed by the subtle interaction of individual cellular receptors, decay accelerating factor (daf) and intercellular adhesion molecule-1 (icam-1). in this receptor complex, daf functions in the membrane sequestration of the virus, while the role of icam-1 is as the functional cellular internalization receptor. however, despite the elucidation of the cva21-cell receptor interactions, there have been few ...200314573809
systemic therapy of malignant human melanoma tumors by a common cold-producing enterovirus, coxsackievirus a21.the incidence of malignant melanoma continues to increase worldwide; however, treatment of metastatic melanoma remains unsatisfactory, and there is an urgent need for development of effective targeted therapeutics. a potential biological target on the surface of malignant melanoma cells is the up-regulated expression of intercellular adhesion molecule (icam)-1 and decay-accelerating factor (daf), relative to surrounding benign tissue. coxsackievirus a21 (a common cold virus) targets and destroys ...200414734451
enhanced cellular receptor usage by a bioselected variant of coxsackievirus a21.decay-accelerating factor (daf) functions as cell attachment receptor for a wide range of human enteroviruses. the kuykendall prototype strain of coxsackievirus a21 (cva21) attaches to daf but requires interactions with intercellular cell adhesion molecule 1 (icam-1) to infect cells. we show here that a bioselected variant of cva21 (cva21-dafv) generated by multiple passages in daf-expressing, icam-1-negative rhabdomyosarcoma (rd) cells acquired the capacity to induce rapid and complete lysis of ...200415507647
interactions of decay-accelerating factor (daf) with haemagglutinating human enteroviruses: utilizing variation in primate daf to map virus binding sites.a cellular receptor for the haemagglutinating enteroviruses (hev), and the protein that mediates haemagglutination, is the membrane complement regulatory protein decay accelerating factor (daf; cd55). although primate daf is highly conserved, significant differences exist to enable cell lines derived from primates to be utilized for the characterization of the daf binding phenotype of human enteroviruses. thus, several distinct daf-binding phenotypes of a selection of hevs (viz. coxsackievirus a ...200414993659
inhibition of proteolytic activity of poliovirus and rhinovirus 2a proteinases by elastase-specific inhibitors.a polyprotein cleavage assay has been developed to assay the proteolytic activities in vitro of the 2a proteinases encoded by poliovirus and human rhinovirus 14, which are representative members of the enterovirus and rhinovirus genera of picornaviruses, respectively. the elastase-specific substrate-based inhibitors elastatinal and methoxysuccinyl-ala-ala-pro-val-chloromethylketone (mpcmk) inhibited both 2a proteinases in vitro. the electrophoretic mobilities of both 2a proteinases were reduced ...19938392608
the crystal structure of coxsackievirus a21 and its interaction with icam-1.cva21 and polioviruses both belong to the enterovirus genus in the family of picornaviridae, whereas rhinoviruses form a distinct picornavirus genus. nevertheless, cva21 and the major group of human rhinoviruses recognize intercellular adhesion molecule-1 (icam-1) as their cellular receptor, whereas polioviruses use poliovirus receptor. the crystal structure of cva21 has been determined to 3.2 a resolution. its structure has greater similarity to poliovirus structures than to other known picorna ...200516004874
a national study on the residential impact of biological aerosols from the land application of biosolids.the purpose of this study was to evaluate the community risk of infection from bioaerosols to residents living near biosolids land application sites.200516033462
gaining target access for deoxyribozymes.antisense oligonucleotides and ribozymes have been used widely to regulate gene expression by targeting mrnas in a sequence-specific manner. long rnas, however, are highly structured molecules. thus, up to 90% of putative cleavage sites have been shown to be inaccessible to classical rna based ribozymes or dnazymes. here, we report the use of modified nucleotides to overcome barriers raised by internal structures of the target rna. in our attempt to cleave a broad range of picornavirus rnas, we ...200415136038
immobilization of antiviral antibody at the cell surface: a novel means for preventing virus infection.methods for preparing bentonite-gamma globulin complexes and for determining their attachment to cells in tissue culture were investigated by use of human immunoglobulin g (igg) labeled with (125)i. for virus-inhibition studies, bentonite-igg complexes were prepared by use of human igg with high specific neutralizing activity against coxsackievirus a21. much of the antibody in the complex remained available for virus neutralization, and the bentonite-igg was at least 500 to 1,000 times as active ...197016557918
a nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice.coxsackievirus a21 (cav21) is classified within the species human enterovirus c (hev-c) of the enterovirus genus of picornaviruses. hev-c share striking homology with the polioviruses (pv), their closest kin among the enteroviruses. despite a high level of sequence identity, cav21 and pv cause distinct clinical disease typically attributed to their differential use of host receptors. pv cause poliomyelitis, whereas cav21 shares a receptor and a propensity to cause upper respiratory tract infecti ...200415353596
oncolysis of vascular malignant human melanoma tumors by coxsackievirus a21.cultured melanoma cell lines despite exhibiting similar in vitro morphology, display significant phenotypic and growth rate differences when propagated as in vivo xenografts. previously we have shown that coxsackievirus a21 (cva21) lytically infects in vitro cultures of malignant melanoma cells and is efficient at reducing the tumor burden of mice bearing slow-growing sk-mel-28 melanoma xenografts. the oncolytic activity of cva21 against in vivo melanoma xenografts, which possess rapid growth ra ...200515870858
oncolytic coxsackievirus a21 as a novel therapy for multiple myeloma.oncolytic viruses are attractive biological agents for the control of human malignancy. this study assessed the capacity of coxsackievirus a21 (cva21) to target and destroy multiple myeloma (mm) and precursor aberrant plasma cells in vitro using established mm cell lines and 15 patient bone marrow (bm) biopsies [n = 10 mm and five monoclonal gammopathy of undetermined significance (mgus)]. cell surface analysis revealed that all tumour cells lines expressed high levels of intercellular adhesion ...200717391493
oncolytic virotherapy for multiple myeloma.current therapies for multiple myeloma (mm) are not curative, thus novel targeted therapeutics are being developed. one such targeted therapy is oncolytic virotherapy, wherein viruses specifically infect and kill the malignant plasma cells, leaving normal cells intact.200818352850
potent oncolytic activity of human enteroviruses against human prostate cancer.oncolytic virotherapy offers a unique treatment modality for prostate cancer, especially stages that are resistant to current therapies, with the additional benefit of preferentially targeting tumor cells amongst an environment of healthy tissue. herein, the low pathogenic enteroviruses; coxsackievirus a21 (cva21), as well as a bio-selected variant of coxsackievirus a21 (cva21-dafv) and echovirus 1 (ev1) are evaluated as novel oncolytic agents against human prostate cancer.200818288643
microrna antagonism of the picornaviral life cycle: alternative mechanisms of interference.in addition to modulating the function and stability of cellular mrnas, micrornas can profoundly affect the life cycles of viruses bearing sequence complementary targets, a finding recently exploited to ameliorate toxicities of vaccines and oncolytic viruses. to elucidate the mechanisms underlying microrna-mediated antiviral activity, we modified the 3' untranslated region (3'utr) of coxsackievirus a21 to incorporate targets with varying degrees of homology to endogenous micrornas. we show that ...201020333250
variation in liposome binding among enteroviruses.liposome-binding properties of native virions and in vitro generated 135s particles of eight enteroviruses were studied. the temperature required for the structural transition from the native 160s virion to a 135s particle was virus-specific, ranging from +38 degrees c to more than +50 degrees c. while the 135s particles of poliovirus 1/mahoney (pv1) and coxsackievirus a21 (cav21) were capable of binding to liposomes, the other viruses showed minimal binding. both of the viruses that bound to li ...200111162809
a whole cell immunization-derived monoclonal antibody that protects cells from coxsackievirus a9 infection binds to both cell surface and virions.coxsackievirus a9 (cav-9) infects human rhabdomyosarcoma (rd) cells using an unidentified rgd-independent receptor. monoclonal antibodies were prepared by immunizing mice with intact rd cells and by selecting cells from the cytopathic effect of cav-9 for protection. here we describe a monoclonal antibody that binds to host cell plasma membrane and protects cells from virus infection. in addition, binding of the virus to cell monolayers was more efficient in the presence of the antibody, suggesti ...200516055201
systemic targeting of metastatic human breast tumor xenografts by coxsackievirus a21.breast cancer is the most commonly diagnosed malignancy in women worldwide. metastatic development is associated with poor prognosis and current therapies provide only limited success. virotherapy is an emerging strategy for the treatment of cancer that utilizes both replication-competent and genetically modified viruses to selectively kill tumor cells. we have previously shown that coxsackievirus a21 (cva21), a wild-type common-cold producing enterovirus, is an effective oncolytic agent against ...200918256929
cell carriers to deliver oncolytic viruses to sites of myeloma tumor growth.multiple myeloma (mm) is a disseminated malignancy of antibody secreting plasma cells that localize primarily to the bone marrow. several studies have illustrated the potential of utilizing oncolytic viruses (measles, vaccinia, vesicular stomatitis virus and coxsackievirus a21) for the treatment of mm, but there are significant barriers that prevent the viruses from reaching sites of myeloma tumor growth after intravenous delivery. the most important barriers are failure to extravasate from tumo ...200818356812
the evolution of vp1 gene in enterovirus c species sub-group that contains types cva-21, cva-24, ev-c95, ev-c96 and ev-c99.genus enterovirus (family picornaviridae,) consists of twelve species divided into genetically diverse types by their capsid protein vp1 coding sequences. each enterovirus type can further be divided into intra-typic sub-clusters (genotypes). the aim of this study was to elucidate what leads to the emergence of novel enterovirus clades (types and genotypes). an evolutionary analysis was conducted for a sub-group of enterovirus c species that contains types coxsackievirus a21 (cva-21), cva-24, en ...201424695547
applications of coxsackievirus a21 in oncology.the clinical management of cancer continues to be dominated by macroscopic surgical resection, radiotherapy, and cytotoxic drugs. the major challenge facing oncology is to achieve more selective, less toxic and effective methods of targeting disseminated tumors, a challenge oncolytic virotherapy may be well-placed to meet. characterization of coxsackievirus a21 (cva21) receptor-based mechanism of virus internalization and lysis in the last decade has suggested promise for cva21 as a virotherapy ...201427512662
coxsackievirus a21, enterovirus 68, and acute respiratory tract infection, china.during august 2006-april 2010, in beijing, china, 2 rare human enterovirus serotypes, coxsackievirus a21 and enterovirus 68, were detected most frequently in human enterovirus-positive adults with acute respiratory tract infections. thus, during some years, these 2 viruses cause a substantial proportion of enterovirus-associated adult acute respiratory tract infections.201222516379
the role of intralesional therapies in melanoma.the us food and drug administration has been rapidly approving new checkpoint inhibitors and targeted therapies for melanoma and other tumors. recently, it approved the first intralesional therapy, talimogene laherparepvec (t-vec), for the treatment of metastatic melanoma lesions in the skin and lymph nodes. several other intralesional therapies (pv-10, interleukin-12 electroporation, coxsackievirus a21 [cva21]) are entering later-stage testing. locally injected agents have clearly shown their a ...201627188674
therapeutic use of native and recombinant enteroviruses.research on human enteroviruses has resulted in the identification of more than 100 enterovirus types, which use more than 10 protein receptors and/or attachment factors required in cell binding and initiation of the replication cycle. many of these "viral" receptors are overexpressed in cancer cells. receptor binding and the ability to replicate in specific target cells define the tropism and pathogenesis of enterovirus types, because cellular infection often results in cytolytic response, i.e. ...201626907330
molecular characterization of coxsackievirus a21 in shandong, china.coxsackievirus a21 (cv-a21) is a rarely detected serotype belonging to the species enterovirus c (ev-c). in this study, we report the isolation and genetic characterization of cv-a21 in shandong province, china, during 1997 to 2013. a total of 13 strains were obtained from surveillance of cases of acute flaccid paralysis (afp) (n = 9) and from environmental sewage (n = 4). sequence comparison of the vp1 genes revealed high nucleotide sequence similarity (94.1 % to 99.8 % identity) among these sh ...201626563316
enhanced oncolysis mediated by coxsackievirus a21 in combination with doxorubicin hydrochloride.virotherapy is an emerging strategy for the treatment of cancer that utilizes both replication-competent and genetically modified viruses to selectively kill tumor cells. we have previously shown that coxsackievirus a21 (cva21), a common-cold producing enterovirus, is an effective oncolytic agent against human melanoma, prostate, and breast cancer xenografts in vivo. cva21 specifically targets and lytically infects susceptible cells expressing the cva21 cellular receptors, intercellular adhesion ...201021170760
the fecal virome of children with hand, foot, and mouth disease that tested pcr negative for pathogenic enteroviruses.hand, foot, and mouth disease (hfmd) affects infant and young children. a viral metagenomic approach was used to identify the eukaryotic viruses in fecal samples from 29 thai children with clinical diagnosis of hfmd collected during the 2012 outbreak. these children had previously tested negative by pcr for enterovirus 71 and coxsackievirus a16 and a6. deep sequencing revealed nine virus families: picornaviridae, astroviridae, parvoviridae, caliciviridae, paramyxoviridae, adenoviridae, reovirida ...201526288145
coxsackievirus a21 synergizes with checkpoint inhibitors.treatment with a combination of a proprietary formulation of coxsackievirus and either an anti-ctla-4 or anti-pd-1 checkpoint inhibitor yielded a higher response rate in phase i testing for melanoma than any of these drugs given on their own. because the viral therapy adds little toxicity, it might prove an effective part of a dual regimen, according to interim trial data presented at the american association for cancer research annual meeting 2017.201728381405
adenovirus type 4 respiratory infections with a concurrent outbreak of coxsackievirus a21 among united states army basic trainees, a retrospective viral etiology study using next-generation sequencing.human adenoviruses (hadv), in particular types 4 and 7, frequently cause acute respiratory disease (ard) during basic military training. hadv4 and hadv7 vaccines reduced the ard risk in u.s. military. it is important to identify other respiratory pathogens and assess their potential impact on military readiness. in 2002, during a period when the hadv vaccines were not available, throat swabs were taken from trainees (nā€‰=ā€‰184) with respiratory infections at fort jackson, south carolina. viral eti ...201728198541
a cluster of coxsackievirus a21 associated acute respiratory illness: the evidence of efficient transmission of cva21.in march 2016, a cluster of unexplained respiratory illnesses was reported by the acute respiratory infections (ari) surveillance system of guangdong province, china. twenty-three high school students and one teacher from the four neighboring classes were admitted to a hospital. cva21 was found in eight of fourteen patients. phylogenetic analysis suggested that the cva21 outbreak was most likely caused by transmission of the virus from person to person. this is the first report of an ari outbrea ...201728025712
oncolysis of malignant human melanoma tumors by coxsackieviruses a13, a15 and a18.many rna viruses are displaying great promise in the field of oncolytic virotherapy. previously, we reported that the picornavirus coxsackievirus a21 (cva21) possessed potent oncolytic activity against cultured malignant melanoma cells and melanoma xenografts in mice. in the present study, we demonstrate that three additional group a coxsackieviruses; coxsackievirus a13 (cva13), coxsackievirus a15 (cva15) and coxsackievirus a18 (cva18), also have similar oncolytic activity against malignant mela ...201121241513
adaptation of an icam-1-tropic enterovirus to the mouse respiratory tract.respiratory tract (rt) infections by members of the enterovirus (ev) genus of the picornaviridae family are the most frequent cause for the common cold and a major factor in the exacerbation of chronic pulmonary diseases. the lack of a practical small-animal model for these infections has obstructed insight into pathogenic mechanisms of the common cold and their role in chronic rt illness and has hampered preclinical evaluation of antiviral strategies. despite significant efforts, it has been di ...201121450825
myeloma xenograft destruction by a nonviral vector delivering oncolytic infectious nucleic acid.the feasibility of using a nonviral vector formulation to initiate an oncolytic viral infection has not been previously demonstrated. we therefore sought to determine whether infectious nucleic acid (ina) could be used in place of virus particles to initiate an oncolytic picornavirus infection in vivo. infectious rna encoding coxsackievirus a21 (cva21) was transcribed from plasmid dna using t7 polymerase. within 48 hours of injecting this rna into kas6/1 myeloma xenografts, high titers of infect ...201121505425
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