| biochemical and genetic studies of the vpg uridylylation reaction catalyzed by the rna polymerase of poliovirus. | the first step in poliovirus (pv) rna synthesis is the covalent linkage of ump to the terminal protein vpg. this reaction can be studied in vitro with two different assays. the simpler assay is based on a poly(a) template and requires synthetic vpg, purified rna polymerase 3d(pol), utp, and a divalent cation. the other assay uses specific viral sequences [cre(2c)] as a template for vpg uridylylation and requires the addition of proteinase 3cd(pro). using one or both of these assays, we analyzed ... | 2003 | 12502805 |
| 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 ... | 2004 | 15136038 |
| human rhinovirus selectively modulates membranous and soluble forms of its intercellular adhesion molecule-1 (icam-1) receptor to promote epithelial cell infectivity. | human rhinoviruses are responsible for many upper respiratory tract infections. 90% of rhinoviruses utilize intercellular adhesion molecule-1 (icam-1) as their cellular receptor, which also plays a critical role in recruitment of immune effector cells. two forms of this receptor exist; membrane-bound (micam-1) and soluble icam-1 (sicam-1). the soluble receptor may be produced independently from the membrane-bound form or it may be the product of proteolytic cleavage of micam-1. the ratio of airw ... | 2003 | 12551926 |
| identification of the human rhinovirus serotype 1a binding site on the murine low-density lipoprotein receptor by using human-mouse receptor chimeras. | human rhinovirus serotype 1a (hrv1a) binds more strongly to the mouse low-density lipoprotein receptor (ldlr) than to the human homologue (m. reithmayer, a. reischl, l. snyers, and d. blaas, j. virol. 76:6957-6965, 2002). here, we used this fact to determine the binding site of hrv1a by replacing selected ligand binding modules of the human receptor with the corresponding ligand binding modules of the mouse receptor. the chimeric proteins were expressed in mouse fibroblasts deficient in endogeno ... | 2004 | 15194751 |
| twelve receptor molecules attach per viral particle of human rhinovirus serotype 2 via multiple modules. | the crystallographic t = 1 (pseudo t = 3) icosahedral symmetry of the human rhinovirus capsid dictates the presence of 60 identical, symmetry related surface structures that are available for antibody and receptor binding. x-ray crystallography has shown that 60 individual very-low density lipoprotein receptor (vldlr) modules bind to hrv2. their arrangement around the fivefold axes of the virion suggested that tandem oligomers of such modules could attach simultaneously to symmetry-related sites ... | 2004 | 15196928 |
| amplicon sequencing and improved detection of human rhinovirus in respiratory samples. | improved knowledge of the genotypic characteristics of human rhinovirus (hrv) is required, as are nucleic detection assays with the capacity to overcome both the similarities between members of the family picornaviridae and the wide diversity of different hrv serotypes. the goal of the present study was to investigate the variability and the genotypic diversity of clinical strains circulating in the community. since most reverse transcription (rt)-pcr assays available cannot differentiate hrv fr ... | 2004 | 15243084 |
| unr is required in vivo for efficient initiation of translation from the internal ribosome entry sites of both rhinovirus and poliovirus. | translation of picornavirus rnas is mediated by internal ribosomal entry site (ires) elements and requires both standard eukaryotic translation initiation factors (eifs) and ires-specific cellular trans-acting factors (itafs). unr, a cytoplasmic rna-binding protein that contains five cold-shock domains and is encoded by the gene upstream of n-ras, stimulates translation directed by the human rhinovirus (hrv) ires in vitro. to examine the role of unr in translation of picornavirus rnas in vivo, w ... | 2003 | 12610110 |
| virus-induced asthma. | clinical and experimental investigations indicate that respiratory viral infections are important triggers for asthma attacks. viral upper respiratory infections have been associated with 80% of asthma exacerbations in children and 50% of all asthma episodes in adults. human rhinovirus (hrv) has been implicated as the most common virus associated with asthma episodes. the observation that the great majority of wheezing lower respiratory tract illnesses in early life are associated with acute vir ... | 2002 | 12619381 |
| human rhinovirus type 2 is internalized by clathrin-mediated endocytosis. | using several approaches, we investigated the importance of clathrin-mediated endocytosis in the uptake of human rhinovirus serotype 2 (hrv2). by means of confocal immunofluorescence microscopy, we show that k(+) depletion strongly reduces hrv2 internalization. viral uptake was also substantially reduced by extraction of cholesterol from the plasma membrane with methyl-beta-cyclodextrin, which can inhibit clathrin-mediated endocytosis. in accordance with these data, overexpression of dynamin k44 ... | 2003 | 12692238 |
| all five cold-shock domains of unr (upstream of n-ras) are required for stimulation of human rhinovirus rna translation. | efficient translation of human rhinovirus-2 (hrv-2) rna from its internal ribosome entry site (ires) depends on the presence of cellular trans-acting factors upstream of n-ras (unr) and polypyrimidine-tract-binding protein. unr contains five cold-shock domains (csds) and is predicted to act as an rna chaperone, allowing the hrv-2 ires to attain the correct conformation for ribosome binding. to investigate the role of each of the csds in ires-dependent translation, five unr mutants, each harbouri ... | 2004 | 15269369 |
| human rhinovirus type 16: mutant v1210a requires capsid-binding drug for assembly of pentamers to form virions during morphogenesis. | our laboratory has previously reported isolation of human rhinovirus type 16 (hrv16) mutants which depend on win 52035 to grow. a rapid rise of progeny virus infectivity occurred when drug was added late in growth cycles, suggesting that the drug-dependence lesion was at the step of virus assembly (w. wang et al., j. virol. 72:1210-1218, 1998). here, we report that capsid subunits, 5s protomers and 14s pentamers, of a drug-dependent mutant were produced normally in the absence of drug, but mutan ... | 2003 | 12743280 |
| the crystal structure of the rna-dependent rna polymerase from human rhinovirus: a dual function target for common cold antiviral therapy. | human rhinoviruses (hrv), the predominant members of the picornaviridae family of positive-strand rna viruses, are the major causative agents of the common cold. given the lack of effective treatments for rhinoviral infections, virally encoded proteins have become attractive therapeutic targets. the hrv genome encodes an rna-dependent rna polymerase (rdrp) denoted 3dpol, which is responsible for replicating the viral genome and for synthesizing a protein primer used in the replication. here the ... | 2004 | 15296746 |
| dynamic force microscopy imaging of native membranes. | we employed magnetic acmode atomic force microscopy (macmode afm) as a novel dynamic force microscopy method to image surfaces of biological membranes in their native environments. the lateral resolution achieved under optimized imaging conditions was in the nanometer range, even when the sample was only weakly attached to the support. purple membranes (pm) from halobacterium salinarum were used as a test standard for topographical imaging. the hexagonal arrangement of the bacteriorhodopsin trim ... | 2003 | 12801675 |
| laue diffraction studies of human rhinovirus 14 and canine parvovirus. | laue diffraction data have been collected from monoclinic crystals of canine parvovirus (cpv), and from cubic crystals of human rhinovirus 14 (hrv14) with and without bound antiviral compounds. in optimal conditions one or two images of hrv14 were sufficient to calculate interpretable electron-density maps of the virus complexes at 3.5 a resolution. the crystals of cpv were of lower symmetry and were more easily damaged by radiation, making it difficult to accumulate a significant amount of usef ... | 1995 | 15299756 |
| a cellular receptor of human rhinovirus type 2, the very-low-density lipoprotein receptor, binds to two neighboring proteins of the viral capsid. | the very-low-density lipoprotein receptor (vldl-r) is a receptor for the minor-group human rhinoviruses (hrvs). only two of the eight binding repeats of the vldl-r bind to hrv2, and their footprints describe an annulus on the dome at each fivefold axis. by studying the complex formed between a selection of soluble fragments of the vldl-r and hrv2, we demonstrate that it is the second and third repeats that bind. we also show that artificial concatemers of the same repeat can bind to hrv2 with th ... | 2003 | 12857919 |
| encephalomyocarditis virus (emcv) proteins 2a and 3bcd localize to nuclei and inhibit cellular mrna transcription but not rrna transcription. | we have followed the viral processing cascade and polyprotein precursor fates during encephalomyocarditis virus (emcv) infection of hela cells using a panel of monoclonal antibodies (mabs). within the first 2-4 h of infection, signals of antibodies specific for the 2a, 3b(vpg), 3c(pro) and 3d(pol) proteins were found to co-localize in nucleoli at the rrna synthesis and cellular protein b23 (nucleophosmin) sites. cellular fractionation identified viral protein precursor 3bcd as the common source ... | 2003 | 12921996 |
| imidazo[1,2-b]pyridazines, novel nucleus with potent and broad spectrum activity against human picornaviruses: design, synthesis, and biological evaluation. | a novel structural class of picornavirus inhibitors comprising an imidazo[1,2-b]pyridazine nucleus was discovered. 2-aminoimidazo[1,2-b]pyridazines (6d, (e/z)-7b, (e)-7d, (z)-7d, (e/z)-8b, (e)-10b, (e)-13a, (z)-13a, (e)-13b, (z)-13b, (e)-13c, and (z)-13c) were designed and synthesized in an effort to identify potent broad spectrum antirhinoviral agents. a practical synthetic route to this chemical scaffold has been developed. the target compounds were evaluated in a plaque reduction assay and in ... | 2003 | 13678411 |
| human rhinovirus capsid dynamics is controlled by canyon flexibility. | quantitative enzyme accessibility experiments using nano liquid chromatography electrospray mass spectrometry combined with limited proteolysis and isotope-labeling was used to examine the dynamic nature of the human rhinovirus (hrv) capsid in the presence of three antiviral compounds, a neutralizing fab, and drug binding cavity mutations. using these methods, it was found that the antivirals win 52084 and picovir (pleconaril) stabilized the capsid, while dansylaziridine caused destabilization. ... | 2003 | 14517058 |
| inhibitors of 3c cysteine proteinases from picornaviridae. | the picornaviridae are among the smallest icosahedral positive-sense single stranded rna containing viruses known, and comprise one of the largest and most important families of human and animal pathogens. the hepatitis a virus (hav) and human rhinovirus (hrv) are important pathogens that belong to the picornavirus family. all picornaviruses have a 3c proteinase that processes an initially biosynthesized precursor protein and is crucial for viral maturation and replication. although it is a cyst ... | 2004 | 15320724 |
| regulation of the cell-cycle-dependent internal ribosome entry site of the pitslre protein kinase: roles of unr (upstream of n-ras) protein and phosphorylated translation initiation factor eif-2alpha. | the pitslre kinases belong to the large family of cyclin-dependent protein kinases. their function has been related to cell-cycle regulation, splicing and apoptosis. we have previously shown that the open reading frame of the p110(pitslre) transcript contains an ires (internal ribosome entry site) that allows the expression of a smaller p58(pitslre) isoform during the g2/m stage of the cell cycle. in the present study we investigated further the role of cis- and trans-acting factors in the regul ... | 2005 | 15330758 |
| discrimination among rhinovirus serotypes for a variant icam-1 receptor molecule. | intercellular adhesion molecule 1 (icam-1) is the cellular receptor for the major group of human rhinovirus serotypes, including human rhinovirus 14 (hrv14) and hrv16. a naturally occurring variant of icam-1, icam-1kilifi, has altered binding characteristics with respect to different hrv serotypes. hrv14 binds to icam-1 only transiently at physiological temperatures but forms a stable complex with icam-1kilifi. conversely, hrv16 forms a stable complex with icam-1 but does not bind to icam-1kilif ... | 2004 | 15331736 |
| rhinovirus 3c protease precursors 3cd and 3cd' localize to the nuclei of infected cells. | human rhinovirus (hrv) 3c protease (3cpro) plays several important roles in the virus replication cycle. this enzyme cleaves the viral polyprotein at discrete sites to produce mature viral proteins and also inhibits cellular rna transcription. it is not clear, however, whether the observed transcriptional shutoff activities are due to 3cpro itself or to 3cpro-containing precursors, and where 3cpro exerts its effects within infected cells. to address these questions hela cells were infected with ... | 2004 | 15448360 |
| structural and virological studies of the stages of virus replication that are affected by antirhinovirus compounds. | pleconaril is a broad-spectrum antirhinovirus and antienterovirus compound that binds into a hydrophobic pocket within viral protein 1, stabilizing the capsid and resulting in the inhibition of cell attachment and rna uncoating. when crystals of human rhinovirus 16 (hrv16) and hrv14 are incubated with pleconaril, drug occupancy in the binding pocket is lower than when pleconaril is introduced during assembly prior to crystallization. this effect is far more marked in hrv16 than in hrv14 and is m ... | 2004 | 15452226 |
| functional conservation of the hydrophobic domain of polypeptide 3ab between human rhinovirus and poliovirus. | in this study we exchanged portions of the poliovirus type 1 (pv1) hydrophobic domain within the membrane-associated polypeptide 3ab for the analogous sequences from human rhinovirus 14 (hrv14). the sequence exchanges were based upon a previous report in which the 22 amino acid hydrophobic region was subdivided into two domains, i and ii, the latter of which was shown to be required for membrane association (j. biol. chem. 271 (1996), 26810). using these divisions, the hrv14 sequences were clone ... | 2003 | 14517095 |
| structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3c protease inhibitors. 8. pharmacological optimization of orally bioavailable 2-pyridone-containing peptidomimetics. | the optimization of the pharmacokinetic performance of various 2-pyridone-containing human rhinovirus (hrv) 3c protease (3cp) inhibitors following oral administration to either beagle dogs or cm-monkeys is described. the molecules described in this work are composed of a 2-pyridone-containing peptidomimetic binding determinant and an alpha,beta-unsaturated ester michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3c enzyme. modificatio ... | 2003 | 14521419 |
| crystal structure of complete rhinovirus rna polymerase suggests front loading of protein primer. | picornaviruses utilize virally encoded rna polymerase and a uridylylated protein primer to ensure replication of the entire viral genome. the molecular details of this mechanism are not well understood due to the lack of structural information. we report the crystal structure of human rhinovirus 16 3d rna-dependent rna polymerase (hrv16 3dpol) at a 2.4-a resolution, representing the first complete polymerase structure from the picornaviridae family. hrv16 3dpol shares the canonical features of o ... | 2005 | 15596823 |
| phase ii, randomized, double-blind, placebo-controlled studies of ruprintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers. | human rhinovirus (hrv) infections are usually self-limited but may be associated with serious consequences, particularly in those with asthma and chronic respiratory disease. effective antiviral agents are needed for preventing and treating hrv illnesses. ruprintrivir (agouron pharmaceuticals, inc., san diego, calif.) selectively inhibits hrv 3c protease and shows potent, broad-spectrum anti-hrv activity in vitro. we conducted three double-blind, placebo-controlled clinical trials in 202 healthy ... | 2003 | 14638501 |
| activity of a type 1 picornavirus internal ribosomal entry site is determined by sequences within the 3' nontranslated region. | we have proposed a cancer treatment modality based on poliovirus chimeras replicating under the translational control of an internal ribosomal entry site (ires) derived from human rhinovirus type 2. insertion of the heterologous ires causes a neuron-specific propagation deficit and eliminates neurovirulence inherent in poliovirus without affecting viral growth in cells derived from malignant gliomas. we now report the elucidation of a molecular mechanism responsible for the cell type-specific de ... | 2003 | 14645707 |
| the human rhinovirus internal cis-acting replication element (cre) exhibits disparate properties among serotypes. | it has been reported previously that the human rhinovirus 14 (hrv-14) rna genome contains a cis-acting replication element (cre) that maps to the capsid coding (p1) sequence [19]. further characterization of the hrv-14 cre in the present study established that by moving the cre stem-loop structure downstream, adjacent to the 3'ncr, that its position is not critical for function. when the p1 sequences of two closely related serotypes of hrv-14 were analyzed for the presence of a cre, both hrv-3 a ... | 2003 | 14648294 |
| small interfering rna molecules as potential anti-human rhinovirus agents: in vitro potency, specificity, and mechanism. | rna silencing or interference (rnai) is a sequence-specific, post-transcriptional process of mrna degradation. the degradation of target gene mrna can be induced by short dsrna molecules (21-25-nt) corresponding to the sequence of the target gene to be silenced. short dsrna molecules have been shown to be very effective in inducing rna silencing in several human cell lines. in this study, we have shown that short dsrna molecules corresponding to the human rhinovirus-16 (hrv-16) genome induce eff ... | 2004 | 14670593 |
| genetic evidence for an interaction between a picornaviral cis-acting rna replication element and 3cd protein. | internally located, cis-acting rna replication elements, termed cres, are essential for replication of the genomes of picornaviruses such as human rhinovirus 14 (hrv-14) and poliovirus because they template uridylylation of the protein primer, vpg, by the polymerase 3d(pol). these cres form stem-loop structures sharing a common loop motif, and the hrv-14 cre can substitute functionally for the poliovirus cre in both uridylylation in vitro and rna replication in vivo. we show, however, that the p ... | 2004 | 14711816 |
| binding of fluorescent dye to genomic rna inside intact human rhinovirus after viral capsid penetration investigated by capillary electrophoresis. | ribogreen is used for concentration measurements of rna. upon binding to the rna, an approximately 1000-fold increase in sensitivity in comparison with the uv absorbance of the free polynucleotide is observed. in the present work, we demonstrate that this dye can penetrate in a time- and temperature-dependent manner the intact viral capsids of human rhinovirus serotypes 2 and 14, where it forms a fluorescent complex with the viral rna. capillary electrophoresis with laser-induced fluorescence de ... | 2004 | 14961716 |
| novel [(biphenyloxy)propyl]isoxazole derivatives for inhibition of human rhinovirus 2 and coxsackievirus b3 replication. | during this study, novel biphenyl derivatives were synthesized and tested for antiviral activity. | 2005 | 15743897 |
| cryoelectron microscopy analysis of the structural changes associated with human rhinovirus type 14 uncoating. | release of the human rhinovirus (hrv) genome into the cytoplasm of the cell involves a concerted structural modification of the viral capsid. the intracellular adhesion molecule 1 (icam-1) cellular receptor of the major-group hrvs and the low-density lipoprotein (ldl) receptor of the minor-group hrvs have different nonoverlapping binding sites. while icam-1 binding catalyzes uncoating, ldl receptor binding does not. uncoating of minor-group hrvs is initiated by the low ph of late endosomes. we h ... | 2004 | 14990711 |
| 2-ethoxybenzoxazole as a bioisosteric replacement of an ethyl benzoate group in a human rhinovirus (hrv) capsid binder. | a series of pyridazinylpiperidinyl capsid-binding compounds with novel bicyclic substituents were synthesized and screened against human rhinovirus (hrv). several 2-alkoxy- and 2-alkylthio-benzoxazole and benzothiazole derivatives showed excellent anti-hrv activity. when tested against a panel of 16 representative hrv types the 2-ethoxybenzoxazole derivative 13 was found to have superior hrv activity (median ec(50) 3.88ng/ml) to known capsid-binders pleconaril and pirodavir. compound 13 illustra ... | 2005 | 15808466 |
| monitoring rna release from human rhinovirus by dynamic force microscopy. | human rhinoviruses were imaged under physiological conditions by dynamic force microscopy. topographical images revealed various polygonal areas on the surfaces of the 30-nm viral particles. rna release was initiated by exposure to a low-ph buffer. the lengths of the rnas that were released but still connected to the virus capsid varied between 40 and 330 nm, whereas rna molecules that were completely released from the virus were observed with lengths up to 1 micro m. fork-like structure element ... | 2004 | 15016841 |
| amino acid changes in proteins 2b and 3a mediate rhinovirus type 39 growth in mouse cells. | many steps of viral replication are dependent on the interaction of viral proteins with host cell components. to identify rhinovirus proteins involved in such interactions, human rhinovirus 39 (hrv39), a virus unable to replicate in mouse cells, was adapted to efficient growth in mouse cells producing the viral receptor icam-1 (icam-l cells). amino acid changes were identified in the 2b and 3a proteins of the adapted virus, rv39/l. changes in 2b were sufficient to permit viral growth in mouse ce ... | 2005 | 15827151 |
| vp1 sequencing of all human rhinovirus serotypes: insights into genus phylogeny and susceptibility to antiviral capsid-binding compounds. | rhinoviruses are the most common infectious agents of humans. they are the principal etiologic agents of afebrile viral upper-respiratory-tract infections (the common cold). human rhinoviruses (hrvs) comprise a genus within the family picornaviridae. there are >100 serotypically distinct members of this genus. in order to better understand their phylogenetic relationship, the nucleotide sequence for the major surface protein of the virus capsid, vp1, was determined for all known hrv serotypes an ... | 2004 | 15016887 |
| human rhinovirus infection induces airway epithelial cell production of human beta-defensin 2 both in vitro and in vivo. | we hypothesized that airway epithelial cells, the primary site of human rhinovirus (hrv) infection, provide a link between the innate and specific immune response to hrv via production of human beta-defensin (hbd)-2, a potent in vitro attractant and activator of immature dendritic cells. infection of primary cultures of human epithelial cells with several hrv serotypes induced expression of hbd-2 mrna and protein, indicating that hbd-2 production was independent of viral receptor usage or mechan ... | 2004 | 15034083 |
| human rhinovirus type 89 variants use heparan sulfate proteoglycan for cell attachment. | we have previously isolated mutants of the major-group human rhinovirus type 89 that grow in cells deficient in intercellular adhesion molecule 1 (icam-1), the receptor used by the wild-type virus for cell entry [a. reischl, m. reithmayer, g. winsauer, r. moser, i. goesler, and d. blaas., j. virol. 75:9312-9319, 2001]. we now demonstrate that one of these variants utilizes heparan sulfate proteoglycan (hspg) as a cellular receptor. adaptation to icam-1-deficient cells not only resulted in the ne ... | 2005 | 15857982 |
| role of nasal nitric oxide in the resolution of experimental rhinovirus infection. | human rhinovirus (hrv) infections are associated with exacerbations of asthma, chronic obstructive pulmonary disease, and sinusitis. nitric oxide (no) might play an important role in host defense through its potent antiviral properties. previous studies have shown that hrv infection in human subjects increased nasal epithelial expression of type 2 nitric oxide synthase (nos2), an isoform of the enzyme that produces no. | 2004 | 15100676 |
| in vitro activity of expanded-spectrum pyridazinyl oxime ethers related to pirodavir: novel capsid-binding inhibitors with potent antipicornavirus activity. | picornaviruses (pv) include human rhinovirus (hrv), the primary cause of the common cold, and the enteroviruses (ev), which cause serious diseases such as poliomyelitis, meningoencephalitis, and systemic neonatal disease. although no compounds for pv infections have been approved in the united states, pirodavir was one of the most promising capsid-binding compounds to show efficacy in human clinical trials for chemoprophylaxis of the common cold. susceptibility to hydrolysis precluded its use as ... | 2004 | 15105133 |
| structure of a monoclonal anti-icam-1 antibody r6.5 fab fragment at 2.8 a resolution. | the specific binding of the monoclonal murine anti-intercellular adhesion molecule-1 (anti-icam-1) antibody, r6.5, inhibits the attachment of neutrophils to endothelium and prevents the attachment of major group human rhinovirus (hrv) to icam-1. this binding interferes with the host immune system and, as a result, the r6.5 antibody has been developed as a therapeutic anti-inflammatory and perhaps anti-hrv agent. the variable-region amino-acid sequence of r6.5 was determined from the anti-icam-1 ... | 1995 | 15299305 |
| inhibition of cellular protein secretion by picornaviral 3a proteins. | during poliovirus infection, anterograde traffic between the endoplasmic reticulum and the golgi is inhibited due to the action of 3a, an 87 amino acid viral protein. the ability of poliovirus protein 3a to inhibit er-to-golgi traffic is not required for virus growth. instead, we have suggested that the inhibition of host protein secretion, shown to reduce the secretion of interferon-beta, il-6, and il-8 and the expression of both newly synthesized mhc class i and tnf receptor in the plasma memb ... | 2005 | 15914217 |
| in vitro antiviral activity and single-dose pharmacokinetics in humans of a novel, orally bioavailable inhibitor of human rhinovirus 3c protease. | (e)-(s)-4-((s)-2-{3-[(5-methyl-isoxazole-3-carbonyl)-amino]-2-oxo-2h-pyridin-1-yl}-pent-4-ynoylamino)-5-((s)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester (compound 1) is a novel, irreversible inhibitor of human rhinovirus (hrv) 3c protease {inactivation rate constant (kobs/[i]) of 223,000 m-1s-1}. in cell-based assays, compound 1 was active against all hrv serotypes (35 of 35), hrv clinical isolates (5 of 5), and related picornaviruses (8 of 8) tested with mean 50% effective concentratio ... | 2005 | 15917520 |
| the minor receptor group of human rhinovirus (hrv) includes hrv23 and hrv25, but the presence of a lysine in the vp1 hi loop is not sufficient for receptor binding. | like all 10 minor receptor group human rhinoviruses (hrvs), hrv23 and hrv25, previously classified as major group viruses, are neutralized by maltose binding protein (mbp)-v33333 (a soluble recombinant concatemer of five copies of repeat 3 of the very-low-density lipoprotein receptor fused to mbp), bind to low-density lipoprotein receptor in virus overlay blots, and replicate in intercellular adhesion molecule 1 (icam-1)-negative cos-7 cells. from phylogenetic analysis of capsid protein vp1-codi ... | 2005 | 15919894 |
| binding of the antiviral drug win51711 to the sabin strain of type 3 poliovirus: structural comparison with drug binding in rhinovirus 14. | the crystal structure of the sabin strain of type 3 poliovirus (p3/sabin) complexed with the antiviral drug win51711 has been determined at 2.9 a resolution. drugs of this kind are known to inhibit the uncoating of the virus during infection, by stabilizing the capsid against receptor-induced conformational changes. the electron density for the bound drug is very well defined so that its position and orientation are unambiguous. the drug binds in a nearly extended conformation, slightly bent in ... | 1995 | 15299834 |
| the role of p38 mapk in rhinovirus-induced monocyte chemoattractant protein-1 production by monocytic-lineage cells. | viral respiratory infections are a major cause of asthma exacerbations and can contribute to the pathogenesis of asthma. major group human rhinovirus enters cells by binding to the cell surface molecule icam-1 that is present on epithelial and monocytic lineage cells. the focus of the resulting viral infection is in bronchial epithelia. however, previous studies of the cytokine dysregulation that follows rhinovirus infection have implicated monocytic lineage cells in establishing the inflammator ... | 2005 | 15944313 |
| enterovirus 68 is associated with respiratory illness and shares biological features with both the enteroviruses and the rhinoviruses. | enterovirus (ev) 68 was originally isolated in california in 1962 from four children with respiratory illness. since that time, reports of ev68 isolation have been very uncommon. between 1989 and 2003, 12 additional ev68 clinical isolates were identified and characterized, all of which were obtained from respiratory specimens of patients with respiratory tract illnesses. no ev68 isolates from enteric specimens have been identified from these same laboratories. these recent isolates, as well as t ... | 2004 | 15302951 |
| a multi-centre pilot proficiency programme to assess the quality of molecular detection of respiratory viruses. | to assess the quality of molecular detection of respiratory viruses in clinical diagnostic laboratories. | 2006 | 16019258 |
| ion transport blockers inhibit human rhinovirus 2 release. | picornavirus replication causes leakage of cytoplasmic k+ and an influx of na+ and ca2+. in this study, we have explored the possibility that a blockade of ca2+ and na+ influx would reduce rhinovirus production and/or release. the ca2+-channel blockers, verapamil and diltiazem, as well as the blocker of na+/h+ exchange and the epithelial na+ channel, eipa, inhibited both virus production and release. the effect on virus release was more pronounced than the effect on production, thus raising the ... | 2005 | 16054245 |
| peripheral genotype-phenotype correlations in asian indians with type 2 diabetes mellitus. | a genome-wide scan of gene expression in leucocytes in asian indians with type 2 diabetes was performed and correlated with their known phenotype. | 2005 | 16121806 |
| viral proteases and phosphorodiesterase inhibitors. | a number of novel drug candidates, which are at different stages of development and various therapeutic targets, mechanisms of action and clinical data were discussed in depth. crystallographic studies and structures of several viral proteases were outlined and described. ag7088 (agouron pharmaceuticals inc) has been developed as a potent, selective human rhinovirus (hrv)3c protease inhibitor, which has now advanced to phase ii trials. vertex pharmaceuticals inc has also made significant progres ... | 1999 | 16127607 |
| high-resolution structure of a picornaviral internal cis-acting rna replication element (cre). | picornaviruses constitute a medically important family of rna viruses in which genome replication critically depends on a small rna element, the cis-acting replication element (cre), that templates 3d(pol) polymerase-catalyzed uridylylation of the protein primer for rna synthesis, vpg. we report the solution structure of the 33-nt cre of human rhinovirus 14 under solution conditions optimal for uridylylation in vitro. the cre adopts a stem-loop conformation with an extended duplex stem supportin ... | 2004 | 15314212 |
| recent advances in rhinovirus therapeutics. | human rhinoviruses are the major causative agents of the common cold. because there are greater than 100 viral serotypes, little immunological protection is afforded to humans by prior rhinovirus exposure, which accounts for the high incidence of infection. in most cases, rhinovirus leads to a short self-limiting illness. however, for asthmatics, the elderly and immunocompromised patients, rhinovirus infection can lead to life-threatening complications. this has spurred a consistent effort over ... | 2004 | 15578974 |
| pharmacophore modeling, docking, and principal component analysis based clustering: combined computer-assisted approaches to identify new inhibitors of the human rhinovirus coat protein. | the development and application of a sophisticated virtual screening and selection protocol to identify potential, novel inhibitors of the human rhinovirus coat protein employing various computer-assisted strategies are described. a large commercially available database of compounds was screened using a highly selective, structure-based pharmacophore model generated with the program catalyst. a docking study and a principal component analysis were carried out within the software package cerius a ... | 2005 | 16190752 |
| [detection of human rhinovirus genes from clinical sample by one-step rt-pcr]. | human rhinovirus (hrv) is the most common respiratory pathogen, which causes not only acute respiratory infection and community acquired pneumonitis in children, but also asthma episode and deterioration. however, the detection of respiratory pathogen, which mainly focuses on respiratory syncytial virus, influenzaviruses a and b, parainfluenza viruses 1-3 and adenoviruses, does not include hrv yet by now in china. the absence of detection method limits the clinical understanding of hrv pathogeni ... | 2005 | 16191293 |
| labeling of capsid proteins and genomic rna of human rhinovirus with two different fluorescent dyes for selective detection by capillary electrophoresis. | during uncoating of human rhinoviruses, the innermost capsid protein vp4 and the genomic rna are released from the viral protein shell. this process gives rise to subviral particles that are composed of the remaining three capsid proteins vp1, vp2, and vp3. the process is believed to take place in a sequential manner in that first vp4 is expelled resulting in a-particles sedimenting at 135s followed by the rna resulting in b-particles sedimenting at 80s. aiming at ultimately analyzing this proce ... | 2004 | 15595880 |
| targacept active conformation search: a new method for predicting the conformation of a ligand bound to its protein target. | targacept active conformation search (tacs) is a novel variation of well-established three-dimensional quantitative structure--activity relationship methodologies that seeks to determine probable conformation(s) of ligands bound to their protein targets. a combination of affinity or activity data and energetically accessible conformational ensembles, each conformer described by three-dimensional (3-d) sensitive descriptors, forms the basis of the tacs data model. recursive pruning is used to red ... | 2004 | 15615532 |
| [rhinovirus diseases: pathogenesis, diagnostics and treatment]. | contemporary data on human rhinovirus diseases and their pathogenesis are presented. special attention is paid to complications which may be caused by rhinovirus infections in allergy-susceptible patients. furthermore, approaches to the diagnostics and treatment of rhinovirus diseases are described. in particular, the advantages of molecular methods for the diagnostics of rhinovirus infection (based on the pcr) in comparison with cultural and immunochemical methods are pointed out. new investiga ... | 2005 | 16279553 |
| a mutation in the first ligand-binding repeat of the human very-low-density lipoprotein receptor results in high-affinity binding of the single v1 module to human rhinovirus 2. | minor group human rhinoviruses (hrvs) bind members of the low-density lipoprotein receptor family for cell entry. the ligand-binding domains of these membrane proteins are composed of various numbers of direct repeats of about 40 amino acids in length. residues involved in binding of module 3 (v3) of the very-low-density lipoprotein receptor (vldlr) to hrv2 have been identified by x-ray crystallography (n. verdaguer, i. fita, m. reithmayer, r. moser, and d. blaas, nat. struct. mol. biol. 11:429- ... | 2005 | 16282473 |
| new treatment regimes for virus-induced exacerbations of asthma. | this review will focus on the role of viruses as causes of asthma exacerbations. the article will briefly review the current literature supporting this view, with a special focus on human rhinovirus (rv), the main virus associated with exacerbations of asthma. the review will then refer to possible strategies for treatment, and will include discussion on treatment with specific anti-viral therapy and type i interferon as a treatment for rv. the review will also include a discussion on current th ... | 2006 | 16289761 |
| antiviral activity of engystol: an in vitro analysis. | to study the effects of the homeopathic preparation engystol (biologische heilmittel heel gmbh, baden-baden, germany) on a panel [corrected] of human pathogenic viruses in vitro. | 2005 | 16296918 |
| nitric oxide and the common cold. | the common cold is a clinical syndrome triggered by a variety of viral pathogens, but rhinoviruses are the most frequent cause. complications of such infections include sinusitis, otitis media, and exacerbations of asthma and chronic obstructive lung disease. there is growing interest in host innate defence responses that may regulate the severity of viral responses. we will review recent evidence that nitric oxide is an important contributor to the host response during colds. | 2005 | 15643342 |
| biopolymer stochastic moments. i. modeling human rhinovirus cellular recognition with protein surface electrostatic moments. | stochastic moments may be applied as molecular descriptors in quantitative structure-activity relationship (qsar) studies for small molecules (h. gonzález-dìaz et al., journal of molecular modeling, 2002, vol. 8, pp. 237-245; 2003, vol. 9, pp. 395-407). however, applications in the field of biopolymers are less known. recently, the march-inside approach has been generalized to encode structural features of proteins and other biopolymers (h. gonzález-dáaz et al., bioinformatics, 2003, vol. 19, pp ... | 2005 | 15648087 |
| age-dependent poliovirus replication in the mouse central nervous system is determined by internal ribosome entry site-mediated translation. | mouse cells are not permissive for the replication of human rhinovirus type 2 (hrv2). to determine the role of the hrv2 internal ribosome entry site (ires) in determining species specificity, a recombinant poliovirus (p1/hrv2) was constructed by substituting the poliovirus ires with the ires from hrv2. this recombinant virus replicated in all human and murine cell lines examined, demonstrating that the hrv2 ires does not limit viral replication in transformed murine cells. p1/hrv2 replicated in ... | 2006 | 16501069 |
| influence of detergent additives on mobility of native and subviral rhinovirus particles in capillary electrophoresis. | the electrophoretic properties of two human rhinovirus (hrv) serotypes, hrv2 and hrv14, their subviral particles, and their capsid proteins were investigated by ce using borate buffer, ph 8.3, as bge and three different detergents as additives. in addition, the influence of modification of the capsid with an amine reactive fluorescent dye, cy3.5, on migration in the electric field was assessed. we found that the reproducibility of the electrophoretic results was decisively dependent on the prese ... | 2006 | 16523456 |
| cell-type-specific repression of internal ribosome entry site activity by double-stranded rna-binding protein 76. | translation of picornavirus plus-strand rna genomes occurs via internal ribosomal entry at highly structured 5' untranslated regions. in addition to canonical translation factors, translation rate is likely influenced by supplementary host and viral trans-acting factors. we previously reported that insertion of a heterologous human rhinovirus type 2 internal ribosomal entry site (ires) into the poliovirus (pv) genome, generating the chimeric virus pv-ripo, selectively abrogates viral translation ... | 2006 | 16537583 |
| rhinoviral infections activate p38map-kinases via membrane rafts and rhoa. | rhinoviral infections belong to the most frequent human infections characterized by common cold, chronic bronchitis, exacerbations of asthma, otitis media and sinusitis. here, we define molecular mechanisms that mediate infections of human epithelial cells with human rhinovirus strain 14 (rv14). we demonstrate that rv14 activates p38-mapkinase (p38-k) in a biphasic time course. early stimulation of p38-k by rv14 was observed a few minutes after initiation of the infection, while the late increas ... | 2006 | 16543732 |
| s-nitrosothiols regulate cell-surface ph buffering by airway epithelial cells during the human immune response to rhinovirus. | human rhinovirus infection is a common trigger for asthma exacerbations. asthma exacerbations and rhinovirus infections are both associated with markedly decreased ph and ammonium levels in exhaled breath condensates. this observation is thought to be related, in part, to decreased activity of airway epithelial glutaminase. we studied whether direct rhinovirus infection and/or the host immune response to the infection decreased airway epithelial cell surface ph in vitro. interferon-gamma and tum ... | 2006 | 16603595 |
| human airway epithelial cells produce ip-10 (cxcl10) in vitro and in vivo upon rhinovirus infection. | human rhinovirus (hrv) infections trigger exacerbations of asthma and chronic obstructive pulmonary disease (copd) and are associated with lymphocytic infiltration of the airways. we demonstrate that infection of primary cultures of human airway epithelial cells, or of the beas-2b human bronchial epithelial cell line, with human rhinovirus type 16 (hrv-16) induces expression of cxcl10 [ifn-gamma-inducible protein 10 (ip-10)], a ligand for the cxcr3 receptor found on activated type 1 t lymphocyte ... | 2005 | 15764644 |
| evidence for functional protein interactions required for poliovirus rna replication. | poliovirus protein 2c contains a predicted n-terminal amphipathic helix that mediates association of the protein with the membranes of the viral rna replication complex. a chimeric virus that contains sequences encoding the 18-residue core from the orthologous amphipathic helix from human rhinovirus type 14 (hrv14) was constructed. the chimeric virus exhibited defects in viral rna replication and produced minute plaques on hela cell monolayers. large plaque variants that contained mutations with ... | 2006 | 16699013 |
| apoptotic events induced by human rhinovirus infection. | hela and 16hbe14o(-) bronchial epithelium cells infected with human rhinovirus serotype 14 (hrv14) were found to exhibit typical apoptotic morphological alterations, such as cell contraction and nuclear condensation. these events coincided with high-molecular-weight dna fragmentation, activation of caspase-9 and caspase-3 and poly(adp-ribose) polymerase cleavage. caspase activation was preceded by cytochrome c translocation from the mitochondria to the cytoplasm, indicating that apoptosis caused ... | 2005 | 15831950 |
| [human rhinovirus detection from infants and young children with acute respiratory infections by nested-polymerase chain reaction]. | to develop a rapid, sensitive and specific method for detection human rhinovirus (hrv) from clinical specimens. | 2006 | 16749999 |
| isatin compounds as noncovalent sars coronavirus 3c-like protease inhibitors. | a series of isatin derivatives were synthesized and tested against sars cov 3c-like protease. substitutions at the n-1 and c-5 positions were examined to elucidate the differences in substrate binding sites of the rhinovirus 3c protease and sars cov 3c-like protease. compound 5f shows significant inhibition with an ic(50) of 0.37 microm. further study showed that, unlike the irreversible covalent binding of isatin derivatives to human rhinovirus 3c protease, the compounds tested in this study ar ... | 2006 | 16759084 |
| crystallographic structural organization of human rhinovirus serotype 16, 14, 3, 2 and 1a. | the architecture of the human rhinovirus is shown to be based on a crystallographic polyhedron (the ico-dodecahedron) with 60 triangular facets and 32 vertices at points of a body-centered icosahedral lattice. the ico-dodecahedron is only slightly different from the t = 3 icosadeltahedron of caspar & klug [cold spring harbor symp. quant. biol. (1962), 27, 1-24]. the capsid of the virion is encapsulated between two ico-dodecahedra in scaling relation by a factor tau, the golden number. clusters w ... | 2006 | 16788267 |
| mode of action of 2-furylmercury chloride, an anti-rhinovirus compound. | 2-furylmercury chloride (2-fmc), an organic mercury derivative, has been found to inhibit the replication of all tested human rhinovirus (hrv) serotypes belonging to the antiviral group b and a limited number of hrv serotypes belonging to the antiviral group a. the mechanism of action of 2-fmc was tested against hrv-2 (antiviral group b, minor receptor group), and compared with an antiviral compound for which the viral target was already determined (enviroxime). 2-fmc was found to bind reversibl ... | 2004 | 15168800 |
| dynamic force microscopy for imaging of viruses under physiological conditions. | dynamic force microscopy (dfm) allows imaging of the structure and the assessment of the function of biological specimens in their physiological environment. in dfm, the cantilever is oscillated at a given frequency and touches the sample only at the end of its downward movement. accordingly, the problem of lateral forces displacing or even destroying bio-molecules is virtually inexistent as the contact time and friction forces are reduced. here, we describe the use of dfm in studies of human rh ... | 2004 | 15243650 |
| respiratory viruses in children younger than five years old with acute respiratory disease from 2001 to 2004 in uberlândia, mg, brazil. | the main viruses involved in acute respiratory diseases among children are: respiratory syncytial virus (rsv), influenzavirus (flu), parainfluenzavirus (piv), adenovirus (adv), human rhinovirus (hrv), and the human metapneumovirus (hmpv). the purpose of the present study was to identify respiratory viruses that affected children younger than five years old in uberlândia, midwestern brazil. nasopharyngeal aspirates from 379 children attended at hospital de clínicas (hc/ufu), from 2001 to 2004, wi ... | 2006 | 16862327 |
| fluorescence labeling of human rhinovirus capsid and analysis by capillary electrophoresis. | the capsid of human rhinovirus serotype 2, consisting of four viral proteins, was fluorescence-labeled with fluorescein isothiocyanate and analyzed by capillary electrophoresis using uv and laser-induced fluorescence detection. heat denaturation, proteolytic digestion, and receptor binding were applied for confirmation of the identity of the peak with the labeled virus. incomplete derivatization with the fluorophore preserved the affinity of the virus for its receptor, indicating that its cell e ... | 2004 | 15253660 |
| human rhinovirus in bronchial epithelium of infants with recurrent respiratory symptoms. | human rhinoviruses (hrvs) are a common cause of upper respiratory tract infections. there is growing evidence that hrvs are also important in lower respiratory tract infections and often induce asthma exacerbations. | 2006 | 16950276 |
| acute otitis media and respiratory viruses. | the present study was performed to elucidate the clinical outcome, and etiology of acute otitis media (aom) in children based on virologic and bacteriologic tests. the study group consisted of 120 children aged 6 to 144 months with aom. middle ear fluid (mef) was tested for viral pathogens by reverse transcriptase polymerase chain reaction (rt-pcr) and for bacteria by gram-staining and culture. clinical response was assessed on day 2 to 4, 11 to 13, 26 to 28. respiratory viruses were isolated in ... | 2007 | 16967296 |
| sequence analysis of human rhinoviruses in the rna-dependent rna polymerase coding region reveals large within-species variation. | human rhinoviruses (hrvs; family picornaviridae), the most frequent causative agents of respiratory infections, comprise more than 100 distinct serotypes. according to previous phylogenetic analysis of the vp4/vp2-coding sequences, all but one of the hrv prototype strains distribute between the two established species, human rhinovirus a (hrv-a) and human rhinovirus b (hrv-b). here, partial sequences of the rna-dependent rna polymerase (3d polymerase)-coding gene of 48 hrv prototype strains and ... | 2004 | 15269368 |
| effects of picornavirus 3a proteins on protein transport and gbf1-dependent cop-i recruitment. | the 3a protein of the coxsackievirus b3 (cvb3), an enterovirus that belongs to the family of the picornaviruses, inhibits endoplasmic reticulum-to-golgi transport. recently, we elucidated the underlying mechanism by showing that cvb3 3a interferes with adp-ribosylation factor 1 (arf1)-dependent cop-i recruitment to membranes by binding and inhibiting the function of gbf1, a guanine nucleotide exchange factor that is required for the activation of arf1 (e. wessels et al., dev. cell 11:191-201, 20 ... | 2006 | 17005635 |
| nonneutralizing human rhinovirus serotype 2-specific monoclonal antibody 2g2 attaches to the region that undergoes the most dramatic changes upon release of the viral rna. | the monoclonal antibody 2g2 has been used extensively for detection and quantification of structural changes of human rhinovirus serotype 2 during infection. it recognizes exclusively a and b subviral particles, not native virus. we have elucidated the basis of this selectivity by determining the footprint of 2g2. since viral escape mutants obviously cannot be obtained, the structures of complexes between fab fragments of 2g2 and 80s subviral b particles were determined by cryoelectron microscop ... | 2006 | 17005641 |
| poliovirus receptor cd155-targeted oncolysis of glioma. | cell adhesion molecules of the immunoglobulin superfamily are aberrantly expressed in malignant glioma. amongst these, the human poliovirus receptor cd155 provides a molecular target for therapeutic intervention with oncolytic poliovirus recombinants. poliovirus has been genetically modified through insertion of regulatory sequences derived from human rhinovirus type 2 to selectively replicate within and destroy cancerous cells. efficacious oncolysis mediated by poliovirus derivatives depends on ... | 2004 | 15279713 |
| human rhinovirus 3c protease: generation of pharmacophore models for peptidic and nonpeptidic inhibitors and their application in virtual screening. | three-dimensional pharmacophore models for peptidic and small organic nonpeptidic inhibitors of the human rhinovirus 3c protease were generated in a structure-based as well as in a ligand-based approach, using the software package catalyst. the inhibitors possess an electrophilic moiety, often a michael acceptor function, which covalently binds to a cysteine in the active site of the enzyme. since this process presents the key step for virus inactivation, the creation of a new function in cataly ... | 2005 | 15921461 |
| understanding human rhinovirus infections in terms of qsar. | the human rhinoviruses (hrvs) are the single most important cause of common colds. the widespread nature of this affliction, the economic consequences, and the well-known impracticality of vaccine development due to the large number of hrv serotypes (>100) have justified the search for chemotherapeutic agents. the interest in the application of quantitative structure-activity relationships has steadily increased in recent decades and we hope it may be useful in the search for anti-hrv agents. in ... | 2007 | 17045322 |
| neutralization of a common cold virus by concatemers of the third ligand binding module of the vldl-receptor strongly depends on the number of modules. | concatemers of various numbers of the third ligand binding repeat of human very-low density lipoprotein receptor arranged in tandem were fused to maltose-binding protein and expressed as soluble polypeptides. these artificial receptors protected hela cells against infection with human rhinovirus serotype 2 (hrv2) to a degree that strongly increased with the number of repeats present; maximal protection was seen for the pentameric concatemer (mbp-v33333). this v3 pentamer neutralized hrv2 more ef ... | 2005 | 15950998 |
| structures of four methyltetrazole-containing antiviral compounds in human rhinovirus serotype 14. | four novel antiviral win compounds, that contain a methyl tetrazole ring as well as isoxazole, pyridazine or acetylfuran rings, have had their structures determined in human rhinovirus serotype 14 at 2.9 a resolution. these compounds bind in the vp1 hydrophobic pocket, but are shifted significantly towards the pocket pore when compared to previously examined win compounds. a putative water network at the pocket pore is positioned to hydrogen bond with these four win compounds, and this network c ... | 1995 | 15299836 |
| transforming growth factor-beta expression induced by rhinovirus infection in respiratory epithelial cells. | rhinovirus infection of the lower airways is now a recognized disease, associated with bronchiolitis and asthma. the bronchial epithelial cells are the host cells when rhinovirus infection occurs in the airway. it was hypothesized that a pro-fibrotic growth factor response may occur in these infected cells, leading to production of a key transforming growth factor, tgf-beta-1. bronchial epithelial cells were inoculated with human rhinovirus and compared at day 1, 3 and 5 to control non-infected ... | 2006 | 17151785 |
| vp4 protein from human rhinovirus 14 is released by pressure and locked in the capsid by the antiviral compound win. | rhinoviruses are the major causative agents of the common cold in humans. here, we studied the stability of human rhinovirus type 14 (hrv14) under conditions of high hydrostatic pressure, low temperature, and urea in the absence and presence of an antiviral drug. capsid dissociation and changes in the protein conformation were monitored by fluorescence spectroscopy, light scattering, circular dichroism, gel filtration chromatography, mass spectrometry and infectivity assays. the data show that h ... | 2007 | 17161425 |
| rapid dna mapping by fluorescent single molecule detection. | dna mapping is an important analytical tool in genomic sequencing, medical diagnostics and pathogen identification. here we report an optical dna mapping strategy based on direct imaging of individual dna molecules and localization of multiple sequence motifs on the molecules. individual genomic dna molecules were labeled with fluorescent dyes at specific sequence motifs by the action of nicking endonuclease followed by the incorporation of dye terminators with dna polymerase. the labeled dna mo ... | 2007 | 17175538 |
| nmr structure of stem-loop d from human rhinovirus-14. | the 5'-cloverleaf of the picornavirus rna genome is essential for the assembly of a ribonucleoprotein replication complex. stem-loop d (sld) of the cloverleaf is the recognition site for the multifunctional viral protein 3cpro. this protein is the principal viral protease, and its interaction with sld also helps to position the viral rna-dependent rna polymerase (3dpol) for replication. human rhinovirus-14 (hrv-14) is distinct from the majority of picornaviruses in that its sld forms a cuaug tri ... | 2007 | 17194719 |
| identification of viruses in patients with postviral olfactory dysfunction. | causative viruses of postviral olfactory dysfunction (pvod) have not yet been identified. the aim of this study was to investigate causative viruses in patients with pvod. | 2007 | 17277621 |
| dynamic force microscopy imaging of plasmid dna and viral rna. | plasmid dna and viral rna were imaged in a liquid environment by dynamic force microscopy (dfm) and fine structures of dna with heights of 1.82+/-0.66 nm were obtained in topographical images. in simultaneously acquired phase images, dna could be imaged with better contrast at lower imaging forces. by splitting the cantilever oscillation signal into lower and upper parts, the contribution of the adhesion between tip and sample to the topographical images was eliminated, resulting in better signa ... | 2007 | 17291581 |
| mimicking early events of virus infection: capillary electrophoretic analysis of virus attachment to receptor-decorated liposomes. | the attachment of human rhinovirus serotype 2 to an artificial cell membrane was followed by capillary electrophoresis. the cell membrane was mimicked by liposomes (average diameter of about 190 nm) containing a lipid with a nitrilotriacetic acid (nta) group. this group, in the presence of ni(2+) ions, served as anchor for the his(6)-tags of recombinant derivatives of the very-low-density lipoprotein (vldl) receptor comprising either modules 1, 2, and 3 (v123) or five tandem copies of module 3 ( ... | 2007 | 17297964 |
| human rhinovirus type 54 infection via heparan sulfate is less efficient and strictly dependent on low endosomal ph. | k-type major-group human rhinoviruses (hrvs) (including hrv54) share a prominent lysine residue in the hi surface loop of vp1 with all minor-group hrvs. despite the presence of this residue, they cannot use members of the low-density lipoprotein receptor family for productive infection. reexamining all k-type viruses for receptor usage, we noticed that hrv54 is able to replicate in rd cells that lack the major-group receptor intercellular adhesion molecule 1 (icam-1). by using receptor blocking ... | 2007 | 17301156 |
| an authentic 3' noncoding region is necessary for efficient poliovirus replication. | picornavirus rna replication involves the specific synthesis of negative-strand intermediates followed by an accumulation of positive-strand viral rna in the presence of a multitude of cellular mrnas. previously, in an effort to identify cis-acting elements required for initiation of negative-strand rna synthesis, we deleted the entire 3' noncoding regions from human rhinovirus and poliovirus genomic rnas. these deletion mutation transcripts displayed a severe delay in rna accumulation following ... | 2005 | 16140772 |
| visualization of single receptor molecules bound to human rhinovirus under physiological conditions. | dynamic force microscopy (dfm) was used to image human rhinovirus hrv2 alone and complexed with single receptor molecules under near physiological conditions. specific and site-directed immobilization of hrv2 on a model cell membrane resulted in a crystalline arrangement of virus particles with hexagonal symmetry and 35 nm spacing. high-resolution imaging of the virus capsid revealed about 20 resolvable structural features with 3 nm diameters; this finding is in agreement with protrusions seen b ... | 2005 | 16154082 |