Publications

virus-mediated release of endosomal content in vitro: different behavior of adenovirus and rhinovirus serotype 2.	endosomal penetration by nonenveloped viruses might be accomplished by either local breakdown of the endosomal membrane (e.g., adenovirus) or formation of a membrane-spanning pore by capsid proteins. uncoating of the nonenveloped virus human rhinovirus serotype 2 (hrv2) has been shown to occur from late endosomes and to be entirely dependent on the acidic ph in this compartment (prchla, e., e. kuechler, d. blaas, and r. fuchs. 1994. j. virol. 68: 3713-3723). to investigate further the mechanism ...	1995	7559769
an antibody fragment from a phage display library competes for ligand binding to the low density lipoprotein receptor family and inhibits rhinovirus infection.	recently antibodies with a wide range of binding specificities have been isolated from large repertoires of antibody fragments displayed on filamentous phage, including those that are difficult to raise by immunization. we have used this approach to isolate an antibody fragment against chicken very low density lipoprotein (vldl) receptor. it binds to the receptor with good affinity (kaff = 2 x 10(8) m-1) as measured by plasmon surface resonance, and competes for binding of natural ligands (vitel ...	1995	7592608
molecular relationships between 21 human rhinovirus serotypes.	we have analysed, by pcr using consensus primers followed by sequencing, 12 human rhinoviruses (hrvs) in a genomic region including that corresponding to the immunogenic site nim-ii. together with published information, 21 sequences are available for comparison. in the region analysed, which encodes 112 amino acids, the majority (18) of the serotypes exhibited at least 70% amino acid identity to one another and some serotypes are very closely related. these include hrv-36, -58 and -89, known to ...	1995	7595358
lower airways inflammatory response during rhinovirus colds.	human rhinovirus (hrv) causes the majority of common colds and possibly also asthma exacerbations. mechanisms linking viruses to changes in airway reactivity are not defined and we hypothesized that changes in endobronchial cell populations may be implicated. bronchial mucosal biopsies taken before, during and after experimental infections with hrv serotype 16 were examined and histamine reactivity was measured in 17 adult volunteers (6 atopic asthmatics). biopsies were examined for mast cells, ...	1995	7613118
[(biaryloxy)alkyl]isoxazoles: picornavirus inhibitors.	a series of biphenyl analogs, 6, of 5-[5-(2,6-dichloro-5-oxazolylphenoxy)pentyl]-3-methylisoxazole (2) have been synthesized and tested in vitro against 10 human rhinovirus serotypes in a tcid50 assay. the most potent compound in the series 6s, 3-[3-[2,6-dimethyl-4-(4-fluorophenyl)-phenoxy]propyl]-3-methylisoxazole , was screened against an additional 84 serotypes. it was found to be active against 64 of the serotypes, while 87 serotypes were sensitive to 2 at < 3 micrograms/ml. on comparison of ...	1995	7629816
poliovirus protease 3c mediates cleavage of microtubule-associated protein 4.	poliovirus infection results in a number of host cell changes, including specific alterations in cellular proteins. this study further characterizes the cleavage of a cytoskeletal protein, microtubule-associated protein 4 (map-4) and investigates the identity of the viral protease which mediates its cleavage. map-4 cleavage by poliovirus was previously identified using a monoclonal antibody (m. joachims and d. etchison, 1992, j. virol. 66, 5997-5804). in this study, map-4 cleavage was found to o ...	1995	7645249
structure of human rhinovirus complexed with fab fragments from a neutralizing antibody.	we have determined the structure of a human rhinovirus (hrv)-fab complex by using cryoelectron microscopy and image reconstruction techniques. this is the first view of an intact human virus complexed with a monoclonal fab (fab17-ia) for which both atomic structures are known. the surface area on hrv type 14 (hrv14) in contact with fab17-ia was approximately 500 a2 (5 nm2), which is much larger than the area that constitutes the nim-ia epitope (on viral protein vp1) defined by natural escape mut ...	1993	7679742
analysis of the human t-cell response to picornaviruses: identification of t-cell epitopes close to b-cell epitopes in poliovirus.	little is known about the nature and specificity of t-cell-mediated responses to picornaviruses in humans. in this study, the nature of the t-cell response to seven picornaviruses, including polioviruses, coxsackieviruses b3 and b4, human rhinovirus 14, and encephalomyocarditis virus, was determined. twenty-nine individuals responded to poliovirus type 3, coxsackievirus b3, and encephalomyocarditis virus by proliferation of t cells, and from such cultures, 130 virus-specific t-cell lines were es ...	1993	7679749
epitope analysis of the t cell response to a complex antigen: proliferative responses to human rhinovirus capsids.	understanding the factors which regulate the repertoire of a t cell response is important when selecting t helper cell epitopes for inclusion in synthetic viral vaccines. in this study we have examined the t cell response to human rhinovirus (hrv) type 1 a in a mouse model system, using a comprehensive set of synthetic peptides which span all four of the proteins which make up the hrv capsid. this constitutes the first study to use a set of peptides covering the entire sequence of all structural ...	1993	7690329
monoclonal antibodies to a peptide of human rhinovirus type 2 with different specificities recognize the same minimum sequence.	monoclonal antibodies (mabs) raised against a synthetic peptide including residues 156-170 of protein vp2 of human rhinovirus type 2 (hrv2) have previously been shown to be of differing specificities. the basis for these differences has now been examined in greater detail by elisa, radioimmunoprecipitation and virus neutralization. reactions with a panel of hrv2 mutant viruses indicated that substitution of some residues could enhance the apparent activity of one of the neutralizing anti-peptide ...	1995	7730811
complete sequence of the rna genome of human rhinovirus 16, a clinically useful common cold virus belonging to the icam-1 receptor group.	we report here the complete nucleotide sequence and predicted polyprotein sequence of hela cell-adapted human rhinovirus 16 (hrv16). this virus is more suitable than human rhinovirus 14 (hrv14) for clinical studies, and its growth and physical properties are favorable for biochemical and crystallographic analysis. the complete message-sense rna genome of hrv16 is composed of 7124 bases, not including the poly(a) tail. an open reading frame, extending from base 626 to 7084 predicts a polyprotein ...	1995	7732663
rna-protein interactions directed by the 3' end of human rhinovirus genomic rna.	the replication of a picornavirus genomic rna is a template-specific process involving the recognition of viral rnas as target replication templates for the membrane-bound viral replication initiation complex. the virus-encoded rna-dependent rna polymerase, 3dpol, is a major component of the replication complex; however, when supplied with a primed template, 3dpol is capable of copying polyadenylated rnas which are not of viral origin. therefore, there must be some other molecular mechanism to d ...	1995	7745708
interaction between the 5'-terminal cloverleaf and 3ab/3cdpro of poliovirus is essential for rna replication.	on the basis of sequence alignments and secondary structure comparisons of the first 100 nucleotides of enterovirus and rhinovirus rnas, chimeric constructs in which this region of poliovirus type 1 mahoney [pv1(m)] is replaced with that of human rhinovirus type 2 (hrv2) or hrv14 have been engineered. these chimeric constructs contain the internal ribosomal entry site of either poliovirus or encephalomyocarditis virus. independent of the internal ribosomal entry site elements, only the construct ...	1995	7745714
localization of human rhinovirus replication in the upper respiratory tract by in situ hybridization.	to localize the sites and determine the extent of human rhinovirus (hrv) replication in the upper respiratory tract, biopsies of nasal and nasopharyngeal epithelia were collected from 26 hrv- or 7 sham-inoculated volunteers on days 1, 3, and 5 and on days 12, 20, or 33 after inoculation and analyzed by in situ hybridization. hrv-infected cells were detected on at least 1 day in 22 of the 23 hrv-infected subjects and in 1 of the 7 sham-inoculated subjects who developed a cold and had nasal secret ...	1995	7751712
a high capacity microbial screen for inhibitors of human rhinovirus protease 3c.	we have developed a high capacity screen for compounds that inhibit the 3c protease of human rhinovirus-1b. the assay uses a recombinant strain of escherichia coli expressing both the protease and a tetracycline resistance-conferring protein modified to contain the minimal protease cleavage site. cultures growing in microtiter plates containing tetracycline are treated with potential inhibitors and simultaneously monitored for change in growth over time using an oxygen probe. most of the culture ...	1994	7765405
a simple model to predict the effectiveness of molecules that block attachment of human rhinoviruses and other viruses.	the binding of viruses to cell surfaces is often mediated by cell surface receptors. the use of soluble receptors, such as intracellular adhesion molecule-1 (icam-1) for human rhinovirus (hrv), cd4 for human immunodeficiency virus (hiv), and cr2 for epstein-barr virus, for in vivo antiviral therapy is under serious investigation. a number of synthetic compounds that affect hrv attachment and uncoating (termed win compounds) are also being studied. however, the mechanism behind the dose-response ...	1995	7766100
kinetics and thermodynamics of virus binding to receptor. studies with rhinovirus, intercellular adhesion molecule-1 (icam-1), and surface plasmon resonance.	we have studied the kinetics and thermodynamics of a virus interacting with its receptor using human rhinovirus serotype 3 (hrv3), soluble intercellular adhesion molecule-1 (icam-1, cd54) containing ig superfamily domains 1-5 (sicam-1), and surface plasmon resonance. there were two classes of binding sites for sicam-1 on hrv3, each comprising about 50% of the total sites, with association rate constants of 2450 +/- 300 and 134 +/- 11 m-1 s-1. these rates are low, consistent with binding to a rel ...	1995	7768920
the antiviral compound enviroxime targets the 3a coding region of rhinovirus and poliovirus.	enviroxime is an antiviral compound that inhibits the replication of rhinoviruses and enteroviruses. we have explored the mechanism of action of enviroxime by using poliovirus type 1 and human rhinovirus type 14 as model systems. by varying the time of drug addition to virus-infected cells, we determined that enviroxime could be added several hours postinfection without significant loss of inhibition. this suggested that the drug targeted a step involved in rna replication or protein processing. ...	1995	7769678
sequence and structural determinants of the interaction between the 5'-noncoding region of picornavirus rna and rhinovirus protease 3c.	it has previously been established that human rhinovirus 14 protease 3c binds specifically to the 5'-noncoding region of the viral rna. a series of mutants of protease 3c and deletion or point mutants of the 5'-noncoding region of the viral rna were analyzed to elucidate the sites of interaction between the protease and the rna. amino acids in protease 3c essential for rna binding were found to be discontinuous in the amino acid sequence, and mutations which destroyed rna binding did not affect ...	1995	7782313
peptide aldehyde inhibitors of hepatitis a virus 3c proteinase.	picornaviral 3c proteinases are a group of closely related thiol proteinases responsible for processing of the viral polyprotein into its component proteins. these proteinases adopt a chymotrypsin-like fold [allaire et al. (1994) nature 369, 72-77; matthews et al. (1994) cell 77, 761-771] and a display an active-site configuration like those of the serine proteinases. peptide-aldehydes based on the preferred peptide substrates for hepatitis a virus (hav) 3c proteinase were synthesized by reducti ...	1995	7794931
rhinovirus-mediated endosomal release of transfection complexes.	endocytosis is an efficient method for transfer of genes into mammalian cells. incorporation of adenovirus particles into gene transfer complexes greatly enhances gene delivery, probably by the release of endocytosed dna into the cytoplasm. we report here that two different serotypes of human rhinovirus (hrv), hrv2 and hrv14, are also able to enhance receptor-mediated gene transfer. the effect of several compounds known to inhibit viral infection on hrv2- and hrv14-enhanced transfection was exam ...	1995	7815487
structures of poliovirus complexes with anti-viral drugs: implications for viral stability and drug design.	picornaviruses, such as the structurally related polioviruses and rhinoviruses, are important human pathogens which have been the target of major drug development efforts. receptor-mediated uncoating and thermal inactivation of poliovirus and rhinovirus are inhibited by agents that bind to each virus by inserting into a pocket in the beta barrel of the viral capsid protein, vp1. this pocket, which is normally empty in human rhinovirus-14 (hrv14), is occupied by an unknown natural ligand in polio ...	1994	7820548
viral cell recognition and entry.	rhinovirus infection is initiated by the recognition of a specific cell-surface receptor. the major group of rhinovirus serotypes attach to intercellular adhesion molecule-1 (icam-1). the attachment process initiates a series of conformational changes resulting in the loss of genomic rna from the virion. x-ray crystallography and sequence comparisons suggested that a deep crevice or canyon is the site on the virus recognized by the cellular receptor molecule. this has now been verified by electr ...	1994	7849588
libraries of human rhinovirus-based hiv vaccines generated using random systematic mutagenesis.	human rhinovirus (hrv), an immunogenic and relatively nonpathogenic virus, has been engineered to display hiv-1 immunogens with the intent of developing a vaccine against aids. hiv immunogens from the v3 loop have been placed into the neutralizing immunogenic (nim) sites on the surface of hrv14 naturally recognized by the immune system. to increase the likelihood of recovering viable chimeras displaying the transplanted hiv-1 v3 loop sequences in conformations that mimic that of hiv, we have use ...	1994	7865333
chimeras from a human rhinovirus 14-human immunodeficiency virus type 1 (hiv-1) v3 loop seroprevalence library induce neutralizing responses against hiv-1.	a chimeric virus library was designed whereby sequences corresponding to the v3 loop of human immunodeficiency virus type 1 (hiv-1) were presented on the surface of human rhinovirus 14. the v3 loop sequences consisted of a relatively conserved segment of seven amino acids and five adjacent residues that were allowed to vary in proportion to their seroprevalence among hiv-1 isolates of north america and europe. a technique called random systematic mutagenesis was used to incorporate the composite ...	1995	7884887
crystallographic and cryo em analysis of virion-receptor interactions.	cryoelectron microscopy has been used to determine the first structure of a virus when complexed with its glycoprotein cellular receptor. human rhinovirus 16 (hrv16) complexed with the two amino-terminal, immunoglobulin-like domains of the intercellular adhesion molecule-1 (icam-1) shows that icam-1 binds into the 12 a deep "canyon" on the surface of the virus. this is consistent with the prediction that the viral receptor attachment site lies in a cavity inaccessible to the host's antibodies. t ...	1994	7913361
pathway of rhinovirus disruption by soluble intercellular adhesion molecule 1 (icam-1): an intermediate in which icam-1 is bound and rna is released.	we have examined the pathway of rhinovirus interaction with soluble intercellular adhesion molecule 1 (sicam-1). binding of sicam-1 to rhinovirus serotypes 3 and 14 gives particles with sedimentation coefficients from 145 to 120s, depending on the amount of sicam-1 bound. the formation of 120s particles is faster and more extensive at a neutral ph than at an acidic ph. a large number of receptors (> 30) can bind to human rhinovirus 3 without disruption. disruption by sicam-1 of rhinovirus that y ...	1994	7914550
the structure of human rhinovirus 16.	rhinoviruses and the homologous polioviruses have hydrophobic pockets below their receptor-binding sites, which often contain unidentified electron density ('pocket factors'). certain antiviral compounds also bind in the pocket, displacing the pocket factor and inhibiting uncoating. however, human rhinovirus (hrv)14, which belongs to the major group of rhinoviruses that use intercellular adhesion molecule-1 (icam-1) as a receptor, has an empty pocket. when antiviral compounds bind into the empty ...	1993	7915182
comparative antirhinoviral activities of soluble intercellular adhesion molecule-1 (sicam-1) and chimeric icam-1/immunoglobulin a molecule.	we conducted a comparative study of the antirhinovirus activities of soluble intercellular adhesion molecule-1 (sicam-1) and a chimeric icam-1/immunoglobulin a (iga) molecule (ici-5d/iga) for nine major receptor group human rhinovirus (hrv) serotypes and for a variant of hrv-39 relatively resistant to inhibition by sicam-1. ici-5d/iga inhibited the infectivity of eight of the nine wild-type hrvs and the resistant hrv-39 variant and was 60 to 170 times more potent than sicam-1 on a molar basis. i ...	1994	7916558
the 2a proteinase of human rhinovirus is a zinc containing enzyme.	the 2a proteinase of human rhinovirus (hrv) 2 is a cysteine proteinase which is not inhibited by metal chelating agents. however, total hydrolysis of highly purified hrv2 2a followed by atom emission spectroscopy demonstrated that hrv2 2a contains 1 mol of zinc per mole of enzyme. furthermore, zn depletion of the enzyme led to a loss of proteolytic activity which could subsequently be restored by zn supplementation.	1994	7941352
an evaluation of the antirhinoviral activity of acetylfuran replacements for 3-methylisoxazoles. are 2-acetylfurans bioisosteres for 3-methylisoxazoles?	as a probe of the 3-methylisoxazole portion of our broad-spectrum antipicornaviral series, a panel of 2-acetylfuran analogues was prepared as replacements for the 3-methylisoxazole ring. comparison of the two series showed remarkable similarity in potency, spectrum of activity, logp, and electrostatic parameters. x-ray studies of 21b bound to human rhinovirus-14 showed that the 2-acetyl group adopted a syn conformation and the carbonyl oxygen acts as a hydrogen bond acceptor with asn219 in much ...	1994	7990117
human rhinovirus 14 complexed with fragments of active antiviral compounds.	crystallographic studies of human rhinovirus 14 (hrv14) crystals soaked with fragments of antiviral win compounds, at high concentrations (82-200 micrograms/ml), show the compounds bind into the hydrophobic beta-barrel (win pocket) of vp1. two of these short compounds (5-[3,5-dimethyl-4-hydroxyphenyl]-2-methyltetrazole and phenol oxazoline) cause conformational changes in the virus similar to the active, longer win compounds. in addition, thermostabilization studies suggest these short win compo ...	1994	8009848
structure determination of an fab fragment that neutralizes human rhinovirus 14 and analysis of the fab-virus complex.	the crystal structure of fab17-ia, an antigen-binding fragment from a murine immunoglobulin that neutralizes human rhinovirus 14 (hrv14), has been solved to 2.7 a resolution. fab17-ia crystallized into three different space groups depending upon the method used to purify the intact antibody. the structure was determined by use of molecular and isomorphous replacement methods. the current model has a crystallographic r-factor of approximately 19% for 10,192 independent reflections between 8 and 2 ...	1994	8027997
development of cowpea mosaic virus as a high-yielding system for the presentation of foreign peptides.	it has recently been shown that cowpea plants can be infected with a cowpea mosaic virus (cpmv) chimera containing an antigenic site from foot-and-mouth disease virus (usha et al., virology 197, 366-374, 1993). analysis of progeny rna produced during such an infection has revealed that the inserted sequence is rapidly lost during serial passaging, probably by a process of homologous recombination. using the information gained from this analysis, we have redesigned the chimeras in such a way that ...	1994	8030255
use of drug-resistance mutants to identify functional regions in picornavirus capsid proteins.	the win drugs and similar hydrophobic compounds that insert into the capsid of picornaviruses have been shown to block viral uncoating. in some of the human rhinoviruses they also block attachment of virus to cells. spontaneously occurring drug-resistant mutants of human rhinovirus 14 and poliovirus type 3 were selected for their ability to make plaques in the presence of the selecting drug. the hrv-14 mutants either prevented drug binding or allowed the virus to attach to cells in the presence ...	1994	8032243
oxadiazoles as ester bioisosteric replacements in compounds related to disoxaril. antirhinovirus activity.	a series of 1,2,4-oxadiazoles has been prepared as ester bioisosteres and tested against 15 human rhinovirus serotypes, and the mic80, the concentration which inhibits 80% or 12 of the serotypes tested, was determined. homologation of the alkyl group attached to the oxadiazole ring resulted in a reduction in activity with increased chain length. introduction of hydrophilic groups in this position rendered the compounds inactive. increasing the length of the side chain attached to the isoxazole r ...	1994	8057290
foot-and-mouth disease virus leader proteinase: purification of the lb form and determination of its cleavage site on eif-4 gamma.	many picornaviruses cause a dramatic decrease in the translation of cellular mrnas in the infected cell, without affecting the translation of their own rna. specific proteolysis of protein synthesis initiation factor eif-4 gamma occurs during infection with rhinoviruses, enteroviruses, and aphthoviruses, apparently leading to an inability of the ribosomes to bind capped mrnas. cleavage of eif-4 gamma in human rhinoviruses and enteroviruses is carried out by the viral 2a proteinase; in aphthoviru ...	1994	8057448
citrinin hydrate and radicinin: human rhinovirus 3c-protease inhibitors discovered in a target-directed microbial screen.		1994	8071130
amplified rhinovirus colds in atopic subjects.	evidence suggests that atopic individuals may be predisposed to more severe rhinoviral colds coupled to a worsening of existing airway disease than those with asthma. the role of atopy and ige levels, as well as their relationship to clinical disease expression have not been defined. we hypothesized that an allergic diathesis modulates rhinoviral colds and have initiated studies of normal, atopic and asthmatic subjects employing experimental rhinoviral infection, with measurements of symptom sco ...	1994	8087657
structure of a human rhinovirus complexed with its receptor molecule.	cryoelectron microscopy has been used to determine the structure of a virus when complexed with its glycoprotein cellular receptor. human rhinovirus 16 complexed with the two amino-terminal, immunoglobulin-like domains of the intercellular adhesion molecule 1 shows that the intercellular adhesion molecule 1 binds into the 12-a deep "canyon" on the viral surface. this result confirms the prediction that the viral-receptor attachment site lies in a cavity inaccessible to the host's antibodies. the ...	1993	8093643
antigen processing and presentation of human rhinovirus to cd4 t cells is facilitated by binding to cellular receptors for virus.	human rhinovirus serotypes (hrv) fall into two distinct groups, major and minor, by virtue of their cell receptor-binding ability. in this study minor receptor-binding group viruses are demonstrated to bind directly to cells of the murine immune system, including lymphoid dendritic cells which act as antigen-presenting cells, although they do not produce a productive infection in murine cells. this binding is specific and can be blocked by other serotypes of minor-group hrv. pre-treatment of hrv ...	1993	8099015
functional studies of truncated soluble intercellular adhesion molecule 1 expressed in escherichia coli.	we have expressed in escherichia coli the two n-terminal immunoglobulin (ig)-like domains of the intercellular adhesion molecule 1 (icam-1). the first 188 residues of icam-1 were expressed with an n-terminal methionine (mp188) or as a maltose-binding fusion protein which was cleaved with factor xa (xp188). after refolding, both mp188 and xp188 were active in binding to the leukocyte integrin lymphocyte function-associated antigen 1, which has previously been shown to bind to the n-terminal ig do ...	1993	8101071
investigation of shape variations in the antibody binding site by molecular dynamics computer simulation.	molecular dynamics simulations have been used to investigate the flexibility and variations in the shape of the binding site of an antibody against human rhinovirus serotype 2 (hrv2) and its complex with a 15 amino acid oligopeptide, the structure of which has been recently determined by x-ray crystallography. during the simulation of the unbound antibody the binding site, defined in terms of the hypervariable regions or complementarity determining regions (cdrs), shows significant fluctuations ...	1994	8120895
members of the low density lipoprotein receptor family mediate cell entry of a minor-group common cold virus.	a protein binding to a minor-group human rhinovirus (hrv2) was purified from hela cell culture supernatant. the amino acid sequences of tryptic peptides showed identity with the human low density lipoprotein (ldl) receptor (ldlr). ldl and hrv2 mutually competed for binding sites on human fibroblasts. cells down-regulated for ldlr expression yielded much less hrv2 upon infection than cells with up-regulated ldlr. virus also bound to the large subunit of the alpha 2-macroglobulin receptor/ldlr-rel ...	1994	8127891
in vitro selection of human rhinovirus relatively resistant to soluble intercellular adhesion molecule-1.	variants of human rhinovirus serotype 39 (hrv-39) relatively resistant to inhibition by soluble intercellular adhesion molecule-1 (sicam-1) were selected by serial passages in hela or wi-38 cells in the presence of sicam-1. moderate resistance (four- to fivefold increases in 50% effective inhibitory concentrations [ec50s]) was observed after the second passage in hela cells and remained constant during six further passages in the presence of 10 micrograms of sicam-1 per ml. a 7- to 17-fold incre ...	1994	8141582
uncoating of human rhinovirus serotype 2 from late endosomes.	the internalization pathway and mechanism of uncoating of human rhinovirus serotype 2 (hrv2), a minor-group human rhinovirus, were investigated. kinetic analysis revealed a late endosomal compartment as the site of capsid modification from d to c antigenicity. the conformational change as well as the infection was prevented by the specific v-atpase inhibitor bafilomycin a1. a requirement for atp was also demonstrated with purified endosomes in vitro. capsid modifications occurred at a ph of 5.5 ...	1994	8189509
crystal structure of a human rhinovirus neutralizing antibody complexed with a peptide derived from viral capsid protein vp2.	the three-dimensional structure of the complex between the fab fragment of an anti-human rhinovirus neutralizing antibody (8f5) and a cross-reactive synthetic peptide from the viral capsid protein vp2 has been determined at 2.5 a resolution by crystallographic methods. the refinement is presently at an r factor of 0.18 and the antigen-binding site and viral peptide are well defined. the peptide antigen adopts a compact fold by two tight turns and interacts through hydrogen bonds, some with ionic ...	1994	8194515
the 5'-untranslated regions of picornavirus rnas contain independent functional domains essential for rna replication and translation.	the role of the 5'-untranslated region (5'utr) in the replication of enteroviruses has been studied by using a series of poliovirus type 3 (pv3) replicons containing the chloramphenicol acetyltransferase reporter gene in which the 5'utr was replaced by the 5'utr of either coxsackievirus b4 or human rhinovirus 14 or composite 5'utrs derived from sequences of pv3, human rhinovirus 14, coxsackievirus b4, or encephalomyocarditis virus. the results indicate that efficient replication of an enteroviru ...	1994	8207812
antipicornavirus activity of tetrazole analogues related to disoxaril.	a series of tetrazole analogues of win 54954, a broad-spectrum antipicornavirus compound, has been synthesized to address the acid lability of the oxazoline ring of this series of compounds. the results of x-ray crystallography studies of several members of the oxazoline series bound to human rhinovirus type 1a and 14 have been used to design compounds in the tetrazole series with a broad spectrum of activity. compound 16b, which has a three-carbon linkage between the isoxazole and phenyl rings ...	1993	8230114
human rhinovirus-14 protease 3c (3cpro) binds specifically to the 5'-noncoding region of the viral rna. evidence that 3cpro has different domains for the rna binding and proteolytic activities.	protease 3c (3cpro) encoded by human rhinovirus type 14 was purified from recombinant escherichia coli and shown to bind specifically to the 5'-terminal 126 nucleotides of the viral rna (126 rna) in addition to efficiently cleaving a synthetic peptide in trans. the binding of 3cpro to the viral rna may be required for the initiation of plus strand viral rna synthesis, suggesting a second non-proteolytic function for 3cpro. single amino acid substitutions were generated in 3cpro at residues that ...	1993	8245010
use of random systematic mutagenesis to generate viable human rhinovirus 14 chimeras displaying human immunodeficiency virus type 1 v3 loop sequences.	random systematic mutagenesis was used to generate a library of human rhinovirus 14 chimeras that each display a segment from the v3 loop of human immunodeficiency virus type 1. the sequence xxigpgraxx, where x could be any of the 20 amino acids, was inserted at the neutralizing immunogenic site ii of human rhinovirus 14 between vp2 residues 159 and 160. twenty-five unique chimeric viruses were isolated, and the identity of their randomized residues was determined. a nonrandom amino acid distrib ...	1994	8254775
detection of human rhinovirus rna in nasal washings by pcr.	a pcr assay was developed to detect human rhinovirus (hrv) rna in nasal washings from individuals experimentally infected with hrv-39 or hrv strain hanks. total rna was purified from samples stored in the presence of vanadyl ribonucleoside complex (vrc) by one of two methods: proteinase k digestion followed by multiple extractions with phenol/chloroform (pk-pc); or denaturation with guanidinium thiocyanate followed by one phenol/chloroform extraction (gtc). the limit of detection of hrv in nasal ...	1993	8264671
2a proteinases of coxsackie- and rhinovirus cleave peptides derived from eif-4 gamma via a common recognition motif.	the cleavage specificities of the 2a proteinases from coxsackievirus b4 (cvb4) and human rhinovirus 2 (hrv2) on oligopeptide substrates have been determined. comparison of the specificity of cvb4 2a proteinase with that of hrv2 2a proteinase allowed cleavable peptides to be designed using the common motif iie/leu-x-thr-x*gly; little resemblance to the viral cleavage site remained. the data also allowed the prediction of three possible cleavage sites for 2a proteinases on eif-4 gamma; two peptide ...	1994	8291255
architecture of the invisible.	from the structure of sodium chloride to that of a human rhinovirus complexed with its receptor--x-ray crystal analysis has taken an extraordinarily fruitful path since its inception 80 years ago.	1993	8336786
comparison of surface properties of picornaviruses: strategies for hiding the receptor site from immune surveillance.	the surface topology and sequence conservation of different picornaviruses have been compared using molecular graphics and statistical analyses. the comparisons suggest that the canyons, surface depressions encircling the fivefold axes, are the sites of receptor attachment of enteroviruses as well as human rhinovirus (hrv). in hrv14, the receptor binding footprint extends beyond the canyon (olson et al. (1993), proc. natl. acad. sci. usa 90, 507-511), but these more exposed regions are not conse ...	1993	8337843
purification of two picornaviral 2a proteinases: interaction with eif-4 gamma and influence on in vitro translation.	a mammalian cell infected with a human rhinovirus or enterovirus has a much reduced capability to translate capped mrnas (the host cell shutoff), while still allowing translation of uncapped viral rna. biochemical and genetic evidence suggests that the viral proteinase 2a induces cleavage of the eukaryotic initiation factor (eif) 4 gamma (also known as p220) component of eif-4 (formerly called eif-4f). however, neither the mechanism underlying the specific proteolysis of eif-4 gamma nor the infl ...	1993	8338854
on the prediction of binding properties of drug molecules by comparative molecular field analysis.	comparative molecular field analysis (comfa) has been applied to three different data sets of drug molecules binding to human rhinovirus 14 (hrv14), thermolysin and renin, respectively. different structural alignments have been tested to predict binding properties. an alignment based on crystallographically determined coordinates of the inhibitors bound to the proteins has been compared with alignments obtained from multiple-fit and field-fit procedures. these methods are commonly used for syste ...	1993	8380615
the nature and spatial distribution of amino acid substitutions conferring resistance to neutralizing monoclonal antibodies in human rhinovirus type 2.	a total of 38 neutralization escape mutant viruses have been selected from a cloned stock of human rhinovirus serotype 2 (hrv-2), using either of two monoclonal antibodies (mabs) which recognize overlapping epitopes as judged by competition binding. the mutant viruses were analysed for their sensitivity to a panel of antiviral mabs by antibody binding and virus neutralization assays. the position and nature of the selected mutations was determined by sequencing of the virus rnas, and the locatio ...	1993	8381460
role of maturation cleavage in infectivity of picornaviruses: activation of an infectosome.	maturation of picornaviruses involves assembly of a "provirion," which undergoes an autocatalytic cleavage of vp0 to vp2 plus vp4. rna transcripts from a cdna clone of human rhinovirus 14 mutated at asparagine 68, one of the residues in the maturation cleavage site, generated normal yields of 150s particles which were noninfectious in the plaque assay because they were unable to initiate a second cycle of infection. these cleavage-defective provirions were otherwise indistinguishable from mature ...	1993	8383233
win 52035-2 inhibits both attachment and eclipse of human rhinovirus 14.	win compounds inhibit attachment of human rhinovirus 14 by binding to a hydrophobic pocket within the capsid and inducing conformational changes in the canyon floor, the region that binds the cellular receptor. to study the basis of drug resistance, we isolated and characterized a family of human rhinovirus 14 mutants resistant to win 52035-2. thermostabilization data and single-cycle growth curves provided evidence for two classes of resistant mutants. one class, here called exclusion mutants, ...	1993	8383239
a comparison of the anti-rhinoviral drug binding pocket in hrv14 and hrv1a.	the three-dimensional structures of two human rhinovirus serotypes (hrv14 and hrv1a) are compared when complexed with various antiviral agents. although these agents all bind into the same hydrophobic pocket, the exact viral-drug interactions differ. in the absence of drugs, the pocket is occupied by a fatty acid in hrv1a, but is empty in hrv14 except for two water molecules. the conformation of each drug is dependent upon the shape of the hydrophobic pocket. in hrv14 the major residues determin ...	1993	8383771
structure determination of antiviral compound sch 38057 complexed with human rhinovirus 14.	sch 38057 (1-[6-(2-chloro-4-methoxyphenoxy)-hexyl]imidazole hydrochloride) is a new, water-soluble antiviral compound that has inhibitory activities against a number of picornavirus infections. the structure of the human rhinovirus 14 (hrv14) complex with sch 38057 was determined at 3.0 a resolution by single-crystal diffraction techniques using synchrotron x-radiation. sch 38057 was found to bind at the innermost end of the hydrophobic pocket within the capsid protein vp1, a locus of binding of ...	1993	8386772
sch 38057: a picornavirus capsid-binding molecule with antiviral activity after the initial stage of viral uncoating.	the activity of a new water-soluble molecule, sch 38057, against picornaviruses is described. sch 38057 inhibited plaque formation of selected entero- and rhinoviruses in a range of 10.2 to 29.1 microm (50% endpoint) and had a therapeutic index of 10 against poliovirus type 2 (polio 2) in hela cells. when administered orally or subcutaneously, sch 38057 protected mice infected with either coxsackievirus b3 (cvb3) or echovirus-9 from mortality. the molecule provided a low level of protection agai ...	1993	8391247
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 ...	1993	8392608
characterization of monoclonal antibodies raised against a synthetic peptide capable of inducing a neutralizing response to human rhinovirus type 2.	synthetic peptides incorporating the derived amino acid sequence of vp2 residues 156 to 170 of human rhinovirus type 2 (hrv2) have previously been shown to elicit antibodies that neutralize virus infectivity. the proportion of virus-reactive antibodies present in polyclonal antisera to these peptides is, however, very low. moreover, neutralization titrations of such antisera correlate poorly with other assays of either anti-virus or anti-peptide activity, suggesting the presence of antibodies wi ...	1993	8393073
structure of a human rhinovirus-bivalently bound antibody complex: implications for viral neutralization and antibody flexibility.	the structure of a neutralizing immunoglobulin (monoclonal antibody mab17-ia), bound to human rhinovirus 14 (hrv14), has been determined by cryo-electron microscopy and image reconstruction. the antibody bound bivalently across icosahedral twofold axes of the virus, and there were no detectable conformational changes in the capsid. thus, bivalently bound iggs do not appear to cause gross deformations in the capsid. differences between the electron density of the constant domains of the bound fab ...	1993	8394005
the involvement of a spliceosome component in internal initiation of human rhinovirus rna translation.	human rhinoviruses (hrvs) and encephalomyocarditis virus (emcv) belong to different genera of the picornavirus family, but the translation of the rnas of both viruses is by the same mechanism, that is, internal ribosome entry. in rabbit reticulocyte lysates this translation initiation is efficient for mrnas bearing the emcv 5' untranslated region (5' utr), but very inefficient for mrnas bearing the hrv 5' utr, unless factors from hela cells are added. the copurification of the hela cell translat ...	1993	8397279
chiral discrimination and antipicornavirus activity of 6-oxazolinylisoflavan.	racemic 6-oxazolinylisoflavan, a highly effective inhibitor of rhinovirus serotype 1b in vitro, was resolved by high-performance liquid chromatography on a chiral stationary phase in order to study the activity of the enantiomers against picornaviruses. the absolute configuration of the two isomers was determined by circular dichroism curves. the antipicornavirus activity of each isomer, separately collected, was evaluated in vitro against human rhinovirus serotype 1b, enterovirus 71, echovirus ...	1993	8398593
rhinoviral receptor discrimination: mutational changes in the canyon regions of human rhinovirus types 2 and 14 indicate a different site of interaction.	amino acid sequence comparisons between the capsid proteins of several human rhinovirus (hrv) serotypes identified residues potentially involved in the discrimination between the major and the minor group receptors. amino acids conserved within minor group hrvs were substituted in a full-length cdna clone of hrv2 for those found at equivalent positions in major group hrvs. transfection of hela cells with rnas transcribed from seven individual mutated cdnas gave rise to only two viable viruses; g ...	1993	8409953
purification of recombinant human rhinovirus 14 3c protease expressed in escherichia coli.	a gene encoding the human rhinovirus 14 (hrv14) sequence for expression of the viral polypeptide protein delta 3abc was inserted into a plasmid driven by the heat-inducible bacteriophage lambda pl promoter. the coding sequence was also inserted into a pet vector for expression in the t7 system to produce 13c, 15n-labeled protein. the expressed hrv14 3c protease (3cpro) autocatalytically cleaved itself from the polyprotein delta 3abc, and the mature hrv14 3cpro partitioned predominantly, in the c ...	1995	8535153
spectroscopic characterization of rhinoviral protease 2a: zn is essential for the structural integrity.	recently, protease 2a of human rhinovirus 2 (hrv2 2a) was shown to require a zinc ion for the formation of an active enzyme although zinc is not involved mechanistically. the data presented clearly show that the zinc ion bound to a picornaviral-specific motif represents an essential component of the native structure, probably representing a new zn-binding motif. this structure, containing mostly beta-strand elements as shown by cd spectroscopy, changes drastically upon removal of zinc. the zinc- ...	1995	8580843
studies on photoinactivation by various phthalocyanines of a free or replicating non-enveloped virus.	the non-enveloped picornaviruses, which are particularly resistant to physicochemical inactivation, include the aetiological agents of poliomyelitis, hepatitis a and e and infectious common cold (rhinovirus). in this work we used human rhinovirus type 5 (rv-5) cultivated in vero cells to study the photoinactivating effects of several phthalocyanines and naphthobenzoporphyrazines. free rv-5 was photoinactivated by aluminium trisulphonated naphthobenzoporphyrazine at 5 x 10(-8) m concentration. th ...	1995	8583283
structure of a neutralizing antibody bound bivalently to human rhinovirus 2.	the structure of a complex between human rhinovirus serotype 2 (hrv2) and the weakly neutralizing monoclonal antibody 8f5 has been determined to 25 a resolution by cryo-electron microscopy and 3-d reconstruction techniques. the antibody is seen to be bound bivalently across the icosahedral 2-fold axis, despite the very short distance of 60 a between the symmetry-related epitopes. the canyon around the 5-fold axis is not obstructed. due to extreme flexibility of the hinge region the fc domains oc ...	1996	8612574
capsid coding sequence is required for efficient replication of human rhinovirus 14 rna.	mechanisms by which the plus-sense rna genomes of picornaviruses are replicated remain poorly defined, but existing models do not suggest a role for sequences encoding the capsid proteins. however, candidate rna replicons (delta p1 beta gal and delta p1luc), representing the sequence of human rhinovirus 14 virus (hrv-14) with reporter protein sequences (beta-galactosidase or luciferase, respectively) replacing most of the p1 capsid-coding region, failed to replicate in transfected h1-hela cells ...	1996	8627720
internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants.	neuropathogenicity of poliovirus can be attenuated by mutations in the internal ribosomal entry site (ires) within the 5' nontranslated region of its genome. the sabin vaccine strains used in prevention of poliomyelitis carry such mutations in their ires elements. in addition, mutations within the structural and nonstructural proteins of sabin strains may equally contribute to the attenuation phenotype. despite their effectiveness as vaccines, the sabin strains retain a neuropathogenic potential ...	1996	8637880
selection of high affinity rna ligands to a synthetic peptide of human rhinovirus 14 coat protein.	we have used the in vitro evolution system (selex) to isolate high affinity rnas which block the canyon region of human rhinovirus 14 (hrv 14). since the genetic diversity of hrv has hampered the development of general anti-rhinovirus vaccines, high affinity rnas may have good advantage for therapeutic application for the human cold.	1995	8643380
synthesis and activity of piperazine-containing antirhinoviral agents and crystal structure of sdz 880-061 bound to human rhinovirus 14.	a series of antipicornaviral agents containing piperazinyl moieties was synthesized with the objective of obtaining a compound with a broad spectrum of antirhinovirus activity, high potency (< or = 0.003 microgram/ml), and low cytotoxicity (> or = 30 micrograms/ml). five compounds of this series were evaluated in detail for efficacy against various hrv serotypes. the agent sdz 880-061, containing the benzothiazine moiety sdz 108-075, which is particularly active against hrv14, and the thiazolyl ...	1996	8648640
proteolytically active 2a proteinase of human rhinovirus 2 is toxic for saccharomyces cerevisiae but does not cleave the homologues of eif-4 gamma in vivo or in vitro.	during the replication of rhino- and enteroviruses, the translation initiation factor elf-4 gamma is specifically cleaved by the virally encoded 2 a proteinase. this cleavage has been proposed to lead to the inability of the host cell to translate its own capped mrna and to stimulate internal initiation of protein synthesis from the viral mrna. however, a direct causal relationship between these effects and 2a proteinase-mediated cleavage of elf-4 gamma has remained difficult to prove, mainly be ...	1996	8659103
structure-infectivity analysis of the human rhinovirus genomic rna 3' non-coding region.	the specific recognition of genomic positive strand rnas as templates for the synthesis of intermediate negative strands by the picornavirus replication machinery is presumably mediated by cis-acting sequences within the genomic rna 3' non-coding region (ncr). a structure-infectivity analysis was conducted on the 44 nt human rhinovirus 14 (hrv14) 3' ncr to identify the primary sequence and/or secondary structure determinants required for viral replication. using biochemical rna secondary structu ...	1996	8668546
comparative susceptibilities of human embryonic fibroblasts and hela cells for isolation of human rhinoviruses.	the recovery of human rhinovirus (hrv) from nasal washings and nasal and pharyngeal swabs from volunteers with naturally acquired colds was compared in different cell types. human embryonic lung fibroblast (helf) strain wi-38 (sensitivity, 61 to 84%) and hela-i, an hrv-susceptible hela clone (sensitivity, 86 to 94%), were the most sensitive cell types used. helf-wi-38 cells showed a cytopathic effect earlier than the other cells used, and the different strains of hrv-susceptible hela cells varie ...	1996	8727918
docking of a human rhinovirus neutralizing antibody onto the viral capsid.	the structure of the complex between the fab fragment of a human rhinovirus serotype 2 (hrv2) neutralizing antibody (8f5) and a cross-reactive synthetic peptide derived from the viral capsid protein vp2 has been recently determined by crystallographic methods. the conformation adopted by the peptide was very similar to and could be superimposed onto the corresponding region of the viral protein vp2 of human rhinovirus 1a (hrv1a) whose three-dimensional structure is known. the structure of the fa ...	1995	8749845
human rhinovirus 2a proteinase mutant and its second-site revertants.	the 2a proteinases of human rhinoviruses are cysteine proteinases with marked similarities to serine proteinases. in the absence of a three-dimensional structure, we developed a genetical screening system for proteolytic activity and identified phe-130 as a key residue. the mutation phe-130-->tyr almost completely inhibited enzyme activity at 37 degrees c; activity was, however, partially restored by the following exchanges: ser-27-->pro, his-135-->arg or his-137-->arg. to investigate this pheno ...	1996	8761474
the poliovirus 135s particle is infectious.	the molecular mechanism of cell entry by unenveloped viruses is poorly understood. the picornaviruses poliovirus, human rhinovirus, and coxsackievirus convert to an altered form (the 135s or a particle) upon interaction with receptors on susceptible cells at 37 degrees c. the 135s particle is thought to be a necessary intermediate because it accumulates inside susceptible cells soon after infection and drugs which inhibit conversion of the virus to this form also prevent infection. however, sinc ...	1996	8794359
neutralizing antibody to human rhinovirus 14 penetrates the receptor-binding canyon.	the three-dimensional structure of intact human rhinovirus 14 (hrv-14) complexed with fab fragments (fab17-ia) from a strongly neutralizing antibody that binds bivalently to the virion has been determined to 4.0 angstrom resolution by a combination of x-ray crystallography and cryo-electron microscopy. in contradiction to the most commonly held model of antibody-mediated neutralization, fab17-ia does not induce a conformational change in the hrv-14 capsid. instead, the paratope of the antibody u ...	1996	8848050
preferential recognition of the very low-density lipoprotein receptor ligand binding site by antibodies from phage display libraries.	screening of a phage library displaying single chain fragments of the variable regions of human immunoglobulins (scfv) for binding to the ovarian chicken very low-density lipoprotein/vitellogenin receptor (ovr) led to the isolation of several antibody fragments with high affinity. as for the natural ligands of ovr, receptor binding of all antibody fragments is strictly ca(2+)-dependent and is prevented by receptor-associated protein (rap). moreover, attachment of human rhinovirus serotype 2 (hrv ...	1996	8906858
risk factors for lower respiratory complications of rhinovirus infections in elderly people living in the community: prospective cohort study.	to assess the role of rhinoviruses in elderly people living in the community.	1996	8916700
investigation on qsar and binding mode of a new class of human rhinovirus-14 inhibitors by comfa and docking experiments.	a 3-d qsar study has been carried out on a new class of potent and selective human rhinovirus-14 (hrv-14) inhibitors. in particular, the comfa (comparative molecular field analysis) technique has been applied to develop a model able to explain and predict the anti-hrv-14 activity of a class of compounds 4 and potentially helpful to design new and more potent antirhinovirus agents. docking experiments have also been performed with the aim of elucidating the possible binding mode of these inhibito ...	1996	8931942
human rhinovirus 3 at 3.0 a resolution.	the over 100 serotypes of human rhinoviruses (hrv) are major causative agents of the common cold in humans. these hrvs can be roughly divided into a major and minor group according to their cellular receptors. they can also be divided into two antiviral groups, a and b, based on their sensitivity to different capsid-binding antiviral compounds. the crystal structures of hrv14 and hrv16, major-receptor group rhinoviruses, as well as hrv1a, a minor-receptor group rhinovirus, were determined previo ...	1996	8939746
rhinovirus inhibits antigen-specific t cell proliferation through an intercellular adhesion molecule-1-dependent mechanism.	to determine whether binding of human rhinovirus (hrv) to intracellular adhesion molecule-1 might disrupt airway immune processes, effects of a major hrv group, hrv-16, on t cell proliferation and cytotoxicity were defined. hrv (1-10 tcid50/cell) significantly inhibited t cell proliferation induced by antigen but not proliferation secondary to mitogens, interleukin-2, or an irradiated allogeneic t cell line. noninfectious (uv-irradiated) hrv had similar effects. inhibition of t cell proliferatio ...	1996	8940202
zinc for treating the common cold: review of all clinical trials since 1984.	all eight publications since 1984 that have reported a total of 10 clinical studies of the treatment of common colds with zinc are reviewed. the reasons for the puzzling mix of diametrically opposite results in these studies are elucidated and related to independent in vitro investigations. a theoretical framework is put forth that explains the beneficial effects of zinc and that has a solid foundation based on the known molecular structures of the surface of human rhinovirus and intercellular a ...	1996	8942045
determination of the pi of human rhinovirus serotype 2 by capillary isoelectric focusing.	capillary isoelectric focusing was applied to determine the pi value of human rhinovirus serotype 2 (hrv 2), a picornavirus of about 8,500,000 da in size. using fused silica capillaries dynamically coated with hydroxypropylmethyl cellulose (added at 0.08% to the catholyte), the virus zone failed to reach the steady state position in the ph gradient within times usually employed in focusing experiments, as the electroosmotic flow (eof) pushed the analyte zone past the detector. therefore, the res ...	1996	8946796
experimental rhinovirus infection in volunteers.	experimental viral disease studies in volunteers have clarified many aspects of the pathogenesis of human viral disease. recently, interest has focused on rhinovirus-associated asthma exacerbations, and new volunteer studies have suggested that airway responsiveness (ar) is enhanced during a cold. for scientific, ethical and safety reasons, it is important to use validated methods for the preparation of a virus inoculum and that the particular virological characteristics and host responses shoul ...	1996	8947068
the development of cowpea mosaic virus as a potential source of novel vaccines.	epitopes from human rhinovirus 14 (hrv-14) and human immunodeficiency virus type (hiv-1) have been expressed on the surface of particles of the plant virus, cowpea mosaic virus (cpmv). the chimaeras retain their ability to grow in plants and large quantities of virions can be easily purified. immunological studies have shown that purified particles have the antigenic properties of the insert, and, in the case of the hiv-1 chimaera, can elicit the production of neutralising antibodies in mice. th ...	1996	8957673
a single amino acid change in protein synthesis initiation factor 4g renders cap-dependent translation resistant to picornaviral 2a proteases.	infection of cells with picornaviruses of the rhino-, aphtho-, and enterovirus groups causes a shut-off in cap-dependent translation of cellular mrnas but permits cap-independent viral rna translation to proceed. this shut-off is thought to be mediated in part by the proteolytic cleavage of eukaryotic initiation factor 4g (eif4g), although there is evidence to the contrary. cleavage of eif4g results in the separation of the eif4e-binding domain from the ribosome- and helicase-binding domains of ...	1996	8961935
design, synthesis, and evaluation of nonpeptidic inhibitors of human rhinovirus 3c protease.	the design, synthesis, and biological evaluation of reversible, nonpeptidic inhibitors of human rhinovirus (hrv) 3c protease (3cp) are reported. a novel series of 2,3-dioxindoles (isatins) were designed that utilized a combination of protein structure-based drug design, molecular modeling, and structure-activity relationship (sar). the c-2 carbonyl of isatin was envisioned to react in the active site of hrv 3cp with the cysteine responsible for catalytic proteolysis, thus forming a stabilized tr ...	1996	8978838
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 ...	1997	8985417
hyper-antigenic variation occurs with human rhinovirus type 17.	of 90 human rhinovirus (rv) serotypes tested, 50 can be placed into 16 groups according to antigenic relationships. it has been suggested that antigenic variants might arise in nature by immunologic pressure. to investigate this possibility, attempts were made to select variants by cloning 16 different plaque-purified rv serotypes in the presence of homologous, polyclonal antisera. isolates were examined for evidence of variation in serum cross-neutralization tests using parental antisera and, i ...	1997	8995661
cations in human rhinoviruses.	all known crystal structures of rhinoviruses have some uninterpreted electron density on their fivefold axes at a distance of about 152 +/- 3 a from the viral center. this density had been assumed to be a ca2+ ion, based on its shape, height, and the presence of ca2+ ions in the crystallization solutions. difference electron density maps between egta-soaked crystals of human rhinovirus 14 (hrv14), as well as hrv16, and their corresponding native structures show that this density is an egta-chela ...	1997	9007054
elf4g and its proteolytic cleavage products: effect on initiation of protein synthesis from capped, uncapped, and ires-containing mrnas.	rhinovirus 2a and foot-and-mouth disease virus lb proteinases stimulate the translation of uncapped messages and those carrying the rhinovirus and enterovirus internal ribosome entry segments (ireses) by a mechanism involving the cleavage of host cell proteins. here, we investigate this mechanism using an artificial dicistronic rna containing the human rhinovirus ires as intercistronic spacer. because both proteinases cleave eukaryotic initiation factor 4g (eif4g), we examined whether the cleava ...	1997	9042945
structure-based design of peptide presentation on a viral surface: the crystal structure of a plant/animal virus chimera at 2.8 a resolution.	we employed a genetically engineered icosahedral plant virus, cowpea mosaic virus (cpmv), as an expression and presentation system to display a 14 amino acid linear antigenic epitope found in a capsid protein of human rhinovirus 14 (hrv14).	1996	9079380