Publications

experimental infections of chimpanzees with human rhinovirus types 14 and 43.		1968	4297694
a subclinical outbreak of human rhinovirus 31 infection in chimpanzees.		1968	4299817
rhinovirus infection of vervet monkeys. a model of human rhinovirus disease.		1969	4310539
in vivo and in vitro synthesis of human rhinovirus type 2 ribonucleic acid.	hela cells infected with human rhinovirus type 2 synthesize a mixture of single-and double-stranded ribonucleic acid (rna). the rna synthesized by the membrane-bound rna polymerase complex in vitro is also a mixture of single- and double-stranded rna, whereas the deoxycholate-treated rna polymerase complex synthesized only double-stranded rna. although twice as much cell-associated viral rna is synthesized in vivo at 34 c than at 37 c, there is no difference in the rate of rna synthesized in vit ...	1972	4339200
failure of a 3-substituted triazinoindole in the prevention of experimental human rhinovirus infection.		1973	4344209
interactions of components of human rhinovirus type 2 with hela cells.		1973	4348300
crystallization of human rhinovirus 1a.		1973	4355113
a comparison of the virus-specific polypeptides of encephalomyocarditis virus, human rhinovirus-1a, and poliovirus.		1973	4357051
comparison of in vitro and cell-mediated alteration of a human rhinovirus and its inhibition by sodium dodecyl sulfate.	after human rhinovirus type 2 (hrv-2) attaches to hela cells, two types of subviral particles are formed which closely resemble particles produced in vitro by acid or heat. one type of particle contains rna whereas the second sediments as an empty capsid and is rna-deficient. sodium dodecyl sulfate (sds) at 10(-4) m inhibits the cell-mediated formation of these particles from hrv-2 virions and the ability of hrv-2 to form plaques, but it does not inhibit the formation of plaques by human rhinovi ...	1973	4359954
antiviral effect of 3, 4-dihydro-1-isoquinolineacetamide hydrochloride in experimental human rhinovirus infection.	double-blind trials were conducted in volunteers to evaluate the efficacy of the prophylactic 3,4-dihydro-1-isoquinolineacetamide hydrochloride (diqa) treatment against rhinovirus type 24 challenge. ten men received a 7-day course of diqa treatment and 11 men received a placebo. the intranasal viral challenge dose was 10 mean tissue culture infective doses. the oral administration of 1 g prechallenge and 2 g a day for 6 consecutive postchallenge days did not prevent the development of colds. nin ...	1973	4367686
antigenic determinants of infective and inactivated human rhinovirus type 2.	treatment of human rhinovirus type 2 (hrv 2) virions at ph 5, at 56 c or in 2 m urea, produces one or both of two types of subviral particles. these subviral particles sediment at 135s or at 80s and both share what have been designated as c-antigenic determinants; the determinants of native virions have been designated d. these sets of determinants have been contrasted by the techniques of immunodiffusion, complement fixation, and serum blocking, and the results indicate that many or most of the ...	1973	4126195
characterization of the large picornaviral polypeptides produced in the presence of zinc ion.	zinc ion inhibits the posttranslational cleavages of human rhinovirus-1a, encephalomyocarditis virus, and poliovirus polypeptides. each virus displayed a different susceptibility to zinc. however, in each case the cleavages of the capsid precursor and the cleavages analogous to the c --> d --> e conversion in encephalomyocarditis virus were most sensitive to zinc. higher concentrations of zinc resulted in the buildup of even larger precursor polypeptides of a size between 106,000 and 214,000 dal ...	1974	4367904
sequential steps in attachment of human rhinovirus type 2 to hela cells.		1974	4372319
preliminary observations pertaining to polyadenylation of rhinovirus rna.	human rhinovirus type 14 contained polyadenylated rna. virus growth in hela cells was inhibited by cordycepin or polyuridilic acid and stimulated by polyadenylic acid. polyadenylic acid also reversed cordycepin inhibition of virus-induced cytopathology of infected hela cells.	1974	4359303
evaluation of isoprinosine in experimental human rhinovirus infection.	the prophylactic efficacy of isoprinosine was evaluated in a double-blind fashion in volunteers challenged with two types of rhinovirus. in the rhinovirus 44 and 32 trials, each of 9 men received a placebo, and eight and 11 men received the drug, respectively. oral isoprinosine, 6 g a day, was given for 2 days prior to intranasal challenge with 100 mean tissue culture infective doses of the virus and for 7 postchallenge days. in both trials the occurrence and severity of colds were greater in th ...	1974	15825396
fractionation of biologically active and inactive populations of human rhinovirus type 2.		1975	163526
the effects of concanavalin a on the early events of infection by rhinovirus type 2 and poliovirus type 2.	the effect of concanavalin a (con a) on the course of early infection of hela cells with purified radioactive human rhinovirus type 2 (hrv-2) or poliovirus type 2 (p-2) has been examined. several early steps in infection were inhibited before the uncoating of parental virus. con a, at 100 mug/ml, reduces attachment of virus when added to cells before infection. con a also detectably slows the normal progression of adsorbed virus to tightly bound forms characterized, in the case of hrv-2, by resi ...	1975	170375
inhibition by zinc of rhinovirus protein cleavage: interaction of zinc with capsid polypeptides.	zinic ions rapidly inhibit virus production in hela cells infected with human rhinovirus type 1a and lead to the accumulation of human rhinovirus type 1a precursor polypeptides. the degree to which cleavage of these precursors is inhibited is directly dependent on the quantity of cell-associated zinc. proteolysis resumes after the removal of zinc-containing medium, and the accumulated viral precursors are cleaved predominantly to stable virus polypeptides. the precursors stabilized at the lowest ...	1976	176466
physical and metabolic requirements for early interaction of poliovirus and human rhinovirus with hela cells.	attachment, ""tight binding'' and eclipse of radioactive poliovirus 2 (p2) and human rhinovirus 2 (hrv 2) were investigated. the activation energy for attachment of both hrv2 and p2 was about 13 kcal/mol. hrv2 differed from p2 in two respects: the arrhenius plot for attachment of hrv2 showed a break at 15 to 19 degrees c when the cells were first treated several hours at 0 degrees c, and attachment of hrv2 was inhibited by treatment of cells with metabolic poisons able to reduce cellular atp by ...	1976	184301
polyadenylate sequences of human rhinovirus and poliovirus rna and cordycepin sensitivity of virus replication.	the polyadenylate [poly(a)] content of the genome rna of human rhinovirus type 14 (hrv-14) is nearly twice as large as that of the genome rna of poliovirus type 2. the poly(a) content of viral rna was determined to be the rnase-resistant fraction of 32p-labeled viral rna extracted from purified virions. polyacrylamide gel electrophoresis indicated that the poly(a) sequences of hrv-14 are more heterogenous and on an average larger than those of poliovirus rna. on the basis of susceptibility to mi ...	1976	185411
picornaviruses: rapid differentiation and identification by immune electronmicroscopy and immunodiffusion.	immune electronmicroscopy (iem) was used to identify human picornaviruses rapidly and to differentiate enteroviruses from rhinoviruses. human sera, diluted 10- to 50-fold beyond the neutralisation endpoints for homologous virus, readily agglutinated c-type antigens of seven human picornaviruses. human sera did not react by iem with a control animal picornavirus. by iem after acid treatment, differentiation of a human enterovirus from a human rhinovirus was possible. there was an excellent correl ...	1977	404426
gel double immunodiffusion studies with sex human rhinoviruses.	rabbits were immunized on six occasions during a seven month period with fluorocarbon and sucrose denstiy gradient purified preparations of human rhinovirus types 1a,2,3,4,9, or 14. sera collected 1 week after the final immunization formed 1 or 2 preciptin lines when reacted by immunodiffusion against fluorocarbon purified preparations of each homologous immunizing virus. heterologous preciptin cross reactions were detected between: rv1a antigen and rabbit sera to rv2, rv9 and rv14; rv2 antigen ...	1978	209768
isolation and genetic analysis of temperature-sensitive mutants of rhinovirus type 2.	temperature-sensitive mutants of human rhinovirus type 2 were isolated by random clonings of mutagenized virus. all mutants were stable. temperature sensitivity was not affected by different host cell systems. complementation was observed in 3 of 10 dual viral mixtures, with complementation indices being as high as 4.0. recombination frequencies fluctuated widely between experiments with different mutants, but positive recombination occurred with mean frequencies ranging from 0.03 to 1.25%. the ...	1980	6250992
persistence of human rhinovirus infectivity under diverse environmental conditions.	the persistence of human rhinovirus type 2 and type 14 infectivity was studied under various laboratory conditions designed to mimic those commonly found in the environment. the effects of temperature, ionic strength, protein content, and evaporation were compared. both viruses were stable (less than 0.3-log decrease in titer) at 6 and 23 degrees c for 24 h in the liquid state regardless of salt or protein additives; a titer decrease of less than 1.0 log was noted at 37 degrees c. however, evapo ...	1981	6261689
purified interferon as protection against rhinovirus infection.	in a double-blind placebo-controlled study a preparation of human leucocyte interferon purified by affinity chromatography using a monoclonal antibody and applied by repeated nasal sprays reduced the incidence and severity of colds in volunteers challenged with human rhinovirus 9. although interferon itself caused some symptoms, these were minor compared with the clinical colds. interferon activity was still detectable in nasal washings as long as 26 hours after the last dose in about half the v ...	1982	6177374
crystallization of a common cold virus, human rhinovirus 14: "isomorphism" with poliovirus crystals.	crystals of rhinovirus 14 have been grown reproducibly. they diffract x-rays to a resolution of at least 3.5 a. the orthorhombic crystal unit cell contains two virions, each situated on a crystallographic twofold axis. at less than 30-a resolution, the space group approximates to 1222 with the particles possessing 222 pseudo crystallographic symmetry. the crystals are "isomorphous" with type i polio crystals [finch, j. t. & klug, a. (1959) nature (london) 183, 1709-1714; hogle, j. m. (1982) j. m ...	1983	6302674
host range mutants of human rhinovirus in which nonstructural proteins are altered.	human rhinovirus type 2 did not replicate in nonpermissive mouse cells; the restriction was not in adsorption but in the early events of virus replication. mutants which had been adapted to grow in mouse cells had the following characteristics: (i) no change in the structural protein, (ii) a larger nonstructural protein and its precursor protein, and (iii) an altered viral rna synthesis. the altered nonstructural proteins correlated with a change in host range of the virus and may be involved in ...	1983	6312099
failure of oral 4',6-dichloroflavan to protect against rhinovirus infection in man.	4',6-dichloroflavan, a potent inhibitor of rhinovirus replication in vitro, was tested in a double-blind placebo controlled volunteer trial for its protective effect against experimental rhinovirus infection. dichloroflavan was given orally (1 mg/kg, 3 times per day) for 3 doses before, and 13 doses after intranasal challenge with rhinovirus type 9, a type known to be highly sensitive in tissue culture. a total of 63 volunteers were included in the analysis for efficacy. dichloroflavan did not p ...	1983	6338868
therapeutic activity of enviroxime against rhinovirus infection in volunteers.	the therapeutic effect of intranasal 2-amino-1-(isopropylsulphonyl)-6-benzimidazole phenyl ketone oxime (enviroxime) against human rhinovirus type 9 was evaluated in a double-blind, placebo-controlled volunteer trial. enviroxime given 6 times a day was well tolerated, producing a reduction in clinical evidence of infection which coincided with the start of medication (44 h after virus challenge). although there was a statistically significant reduction in clinical score in the enviroxime group o ...	1983	6870216
pharmacokinetics of intranasally applied medication during a cold.	the rate at which interferon is cleared from the nose after local administration was measured in volunteers both before and after challenge with virulent strains of human rhinovirus. interferon was not cleared more rapidly after virus challenge, and there was no relationship between the amount of nasal secretion produced after challenge, and the rate of interferon clearance. these findings suggest that an inverse relationship between the quantity of a locally applied antirhinovirus drug which is ...	1984	6742821
radiochemical determination of polyamines in poliovirus and human rhinovirus 14.	hela cells were made strictly dependent upon polyamine by growth in the presence of alpha-difluoromethylornithine, a specific inhibitor of ornithine decarboxylase. under these conditions, the specific activity of the cellular polyamine pools eventually equilibrated to that of exogenously supplied [14c]putrescine; however, the process was very slow, requiring half-equilibration times of about 16 h for spermidine and 28 for spermine. thus, the distribution of radioactivity in individual polyamines ...	1984	6323434
na and k changes in animal virus-infected hela cells.	na-k changes and cytotoxic effects were monitored in hela cells infected with encephalomyocarditis (emc) virus, human rhinovirus or vesicular stomatitis virus (vsv). whereas in all three cases na-k changes followed viral inhibition of cellular protein synthesis, such changes preceded trypan blue staining of rhinovirus-infected or vsv-infected cells and paralleled trypan blue staining of emc virus-infected cells. in each case a progressive reduction in cellular electrical volume was associated wi ...	1984	6327896
relationship of human rhinovirus strain 2 and poliovirus as indicated by comparison of the polymerase gene regions.	cdna clones representing the 3'-terminal region of the human rhinovirus strain 2 genome have been obtained. the sequence of 1425 nucleotides adjacent to the poly(a) tract is presented and contains an open reading frame of 1383 nucleotides. the derived amino acid sequence corresponding to the putative rna polymerase-coding region is compared to those of poliovirus type 1 (mahoney) and foot-and-mouth disease virus a12. a high degree of homology between human rhinovirus strain 2 and poliovirus type ...	1984	6330989
many rhinovirus serotypes share the same cellular receptor.	twenty-four human rhinovirus serotypes were grown and purified by centrifugation in metrizamide density gradients. these preparations had a lower buoyant density (1.24 g/cm3) and higher specific infectivities (1:24 to 1:240) than did rhinoviruses described previously (e. j. stott and r. j. killington, annu. rev. microbiol. 26:503-524, 1972). binding conditions in which the unique cellular receptors for virus attachment were saturated were determined for each serotype. competition binding assays ...	1984	6086949
virion orientation in cubic crystals of the human common cold virus hrv14.	a new cubic crystal form (a = 445.1 a) of space group p23 is reported for human rhinovirus r14. there are four particles per unit cell, each situated on a crystallographic 3-fold axis. the orientation of these particles has been determined with a rotation function and their approximate positions have been derived from a patterson map. the crystals diffract to at least 2.8 a resolution. limitations to the possible surface features of the virus are set by a comparison of the cubic and orthorhombic ...	1984	6088778
the complete nucleotide sequence of a common cold virus: human rhinovirus 14.	the complete nucleotide sequence of the single-stranded rna genome of human rhinovirus 14, one of the causative agents of the common cold, has been determined from cdna cloned in e. coli. the genome is typical of the picornaviridae family, comprising a 5' non-coding region of 624 nucleotides, a long open reading frame of 6537 nucleotides (90.8% of the genome) and a 3' non-coding region of 47 nucleotides. comparison of the nucleotide sequence and the predicted amino acid sequence with those of th ...	1984	6093056
structure of the mengo virion. vii. crystallization and preliminary x-ray diffraction analysis.	crystals of mengo virions have been grown reproducibly and analyzed by x-ray diffraction. these crystals diffract to a resolution of 7.0 a. the unit cell exhibits cubic symmetry with a = 422 a. the space group is p23, with four virus particles situated on crystallographic threefold axes. picornavirions from three of the four recognized genera (study group on picornaviridae, intervirology 10, 165-180, 1978) have now been examined at low resolution by x-ray diffraction: poliovirus type 1 (j. t. fi ...	1984	6093358
evaluation of the antirhinovirus chalcone ro 09-0415 given orally to volunteers.	ro 09-0415, a phosphorylated 'pro-drug' of the potent antirhinovirus compound, 4' ethoxy-2'-hydroxy-4, 6' dimethoxy-chalcone (ro 09-0410) was tested in a double-blind placebo-controlled trial for its protective effect against experimental rhinovirus infection. the maximum dose, 1200 mg bd, based on considerations of practicality and tolerance was given orally both before and after challenge with a sensitive rhinovirus, type 9. plasma concentrations of active compound in excess of those required ...	1984	6094423
different ph requirements for entry of the two picornaviruses, human rhinovirus 2 and murine encephalomyocarditis virus.	the entry into cells of human rhinovirus 2 (hrv 2) and murine encephalomyocarditis (emc) virus was studied by the use of light-sensitive virus grown in the presence of acridine orange (hrv 2) and neutral red (emc). hela cells were protected against infection with hrv 2 by nh4cl, monensin, and other compounds known to increase the ph of intracellular vesicles. preincubation of the cells with the same compounds reduced the ability of the cells to bind [35s]methionine-labeled hrv 2, apparently due ...	1984	6097029
antivirus agent, ro 09-0410, binds to rhinovirus specifically and stabilizes the virus conformation.	the antiviral mechanisms of ro 09-0410 (4'-ethoxy-2'-hydroxy-4,6'-dimethoxychalcone), which inactivates rhinovirus exclusively, have been investigated. it was suggested that ro 09-0410 bound to human rhinovirus type 2 (hrv-2) and made it inactive, since the reduced infectivity was completely restored to original levels by extraction of the agent with chloroform [h. ishitsuka, y. ninomiya, c. ohsawa, m. fujiu, and y. suhara (1982) antimicrob. agents chemother. 22, 617-621]. this was confirmed usi ...	1984	6100571
preliminary characterization of a persistent infection of hela cells with human rhinovirus type 2.	we were able to initiate a persistent infection (pi) in hela cells with a temperature-sensitive (ts-) mutant of rhinovirus type 2 (ts-1), but not with the corresponding wildtype (wt) virus. the ability to initiate a pi may be related to the multiplicity of infection. persistence was established at 37 degrees c but not at 32 degrees c and the virus isolated from the pi was no longer temperature-sensitive. infectious virus was continually produced at low levels throughout the course of the pi and ...	1985	2578551
replication of human rhinovirus serotypes in a cell line derived from the brain of hamster embryo.		1985	2869665
evidence for at least two dominant neutralization antigens on human rhinovirus 14.	a collection of 28 mutants of human rhinovirus 14, selected for resistance to 10 individual neutralizing monoclonal antibodies, was used to identify two major neutralization antigens, n-ag i and n-ag ii. isoelectric analysis showed that all 16 of the n-ag i mutants analyzed were charge altered in vp1;8 of 12 n-ag ii mutants were altered in vp3. these results suggest that n-ag i resides on vp1, whereas n-ag ii lies on vp3. the frequency of charge alterations was much higher than predicted by the ...	1985	2981332
purification of a soluble template-dependent rhinovirus rna polymerase and its dependence on a host cell protein for viral rna synthesis.	the soluble phase of the cytoplasm of human rhinovirus type 2-infected cells contains an enzymatic activity able to copy rhinovirion rna without an added primer. this rna-dependent rna polymerase (replicase) makes a specific copy of the added rhinovirion rna, as shown by hybridization of the product to its template rna but not to other rnas. the same replicase preparation also contains a virus-specific polyuridylic acid [poly(u)] polymerase activity which is dependent on added polyadenylic acid- ...	1985	2981346
molecular cloning and complete sequence determination of rna genome of human rhinovirus type 14.	the genomic rna of human rhinovirus type 14 was cloned in escherichia coli and the complete nucleotide sequence was determined. the rna genome is 7212 nucleotides long. a single large open reading frame of 6536 nucleotides was identified, which starts at nucleotide 678 and ends 47 nucleotides from the 3' end of the rna genome. comparisons of the specified proteins with those of other picornaviruses showed a striking homology (44-65%) between rhinovirus and poliovirus. the rhinovirus genomic rna ...	1985	2983312
human rhinovirus 14 infection of hela cells results in the proteolytic cleavage of the p220 cap-binding complex subunit and inactivates globin mrna translation in vitro.	one of the characteristics of picornavirus infection of cells in tissue culture is a specific inhibition of utilization of host cell mrna for protein synthesis. in this study we show that human rhinovirus 14 is similar to poliovirus in that the inhibition of host cell translation that occurs during infection correlates with the proteolytic cleavage of an mr 220,000 subunit of the cap-binding protein complex.	1985	2985827
human rhinovirus 2: complete nucleotide sequence and proteolytic processing signals in the capsid protein region.	cdna clones representing the entire genome of human rhinovirus 2 have been obtained and used to determine the complete nucleotide sequence. the genome consists of 7102 nucleotides and possesses a long open reading frame of 6450 nucleotides; this reading frame is initiated 611 nucleotides from the 5' end and stops 42 nucleotides from the polya tract. the n-terminal sequences of three of the viral capsid proteins have been elucidated, thus defining the positions of three cleavage sites on the poly ...	1985	2987843
comparative studies on the modes of action of the antirhinovirus agents ro 09-0410, ro 09-0179, rmi-15,731, 4',6-dichloroflavan, and enviroxime.	modes of action of five antirhinovirus agents were compared. ro 09-0410, 4',6-dichloroflavan, and rmi-15,731 were active preferentially against human rhinovirus. serotypes of the virus varied in their susceptibility to these three agents, whereas ro 09-0179 and enviroxime showed activity against all the serotypes of the virus tested to date. ro 09-0410, rmi-15,731, and 4',6-dichloroflavan inactivated the virus directly, although 4',6-dichloroflavan did so only slightly. inactivation by 4',6-dich ...	1985	2988431
studies on 44 081 r.p., a new antirhinovirus compound, in cell cultures and in volunteers.	a synthetic compound, 2-[(1,5,10,10a-tetrahydro-3h-thiazolo[3,4b]isoquinolin-3-ylidene) amino]-4-thiazoleacetic acid (s), 44 081 r.p., inhibits the multiplication of rhinoviruses in cell cultures. of the 69 rhinovirus strains and serotypes that have been studied, 39% were inhibited at a concentration of 7 micrograms/ml, far below that which affects cellular metabolism (250 micrograms/ml). preliminary data indicate that the compound inhibits some early events of virus replication but that some ce ...	1985	2990329
structure of a human common cold virus and functional relationship to other picornaviruses.	we report the first atomic resolution structure of an animal virus, human rhinovirus 14. it is strikingly similar to known icosahedral plant rna viruses. four neutralizing immunogenic regions have been identified. these, and corresponding antigenic sequences of polio and foot-and-mouth disease viruses, reside on external protrusions. a large cleft on each icosahedral face is probably the host cell receptor binding site.	1985	2993920
in vitro synthesis of an infectious rna from cdna clones of human rhinovirus type 14.	development of a novel infectious cdna assay is described for human rhinovirus type 14. a full-length cdna clone of the human rhinovirus type 14 genome rna was assembled and transcribed in vitro by using the sp6 transcription system. transfection of hela cells with the nascent rna resulted in the production of rhinovirus indistinguishable from the parental virus by both immunological and polyacrylamide gel analysis.	1985	2997483
entry mechanisms of protein toxins and picornaviruses.	the mode of entry into cells of a number of protein toxins with intracellular sites of action and of three picornaviruses is discussed. of the different toxins in this group, diphtheria toxin has been most thoroughly studied with respect to its uptake mechanism. this toxin binds to cell surface receptors which are possibly part of the major anion-transport system in the cells. the bound toxin is then endocytosed and, when the ph drops below ph 5, a normally hidden hydrophobic domain is exposed a ...	1985	3915869
isolation of a monoclonal antibody that blocks attachment of the major group of human rhinoviruses.	reciprocal competition binding assays have previously demonstrated that 20 of 24 human rhinovirus serotypes tested compete for a single cellular receptor. these studies suggested that the vast majority of rhinovirus serotypes utilize a single cellular receptor. with hela cells as an immunogen, a mouse monoclonal antibody was isolated which had the precise specificity predicted by the competition binding study. the receptor antibody was shown to protect hela cells from infection by 78 of 88 human ...	1986	3001366
human rhinovirus protein synthesis and polyprotein cleavage in infected hela-rh cells. brief report.	precursor and mature polypeptides of four human rhinovirus types (hrv 30, 63, 81 and 88) were compared. the sds-page profiles of the hrv-specific polypeptides differed significantly from each other, as well as from those of the hrv types studied previously (hrv 1a, 2 and 14). our results provide further evidence for considerable heterogeneity within the rhinovirus genus.	1986	3015086
the site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating.	win 51711 and win 52084 are structurally related, antiviral compounds that inhibit the replication of rhino (common cold) viruses and related picornaviruses. they prevent the ph-mediated uncoating of the viral rna. the compounds consist of a 3-methylisoxazole group that inserts itself into the hydrophobic interior of the vp1 beta-barrel, a connecting seven-membered aliphatic chain, and a 4-oxazolinylphenoxy group (op) that covers the entrance to an ion channel in the floor of the "canyon." viral ...	1986	3018924
prevention of rhinovirus and poliovirus uncoating by win 51711, a new antiviral drug.	win 51711, a potent new antipicornavirus drug, has been shown to inhibit an early event in the replication cycle of human poliovirus type 2 and human rhinovirus type 2. win 51711 was not virucidal and had no measurable effect on the adsorption of [3h]uridine-labeled virions to cells. when virion penetration of the plasma membrane was determined through loss of sensitivity to neutralizing antisera, win 51711 had no effect on poliovirus penetration, but inhibited rhinovirus penetration by 40%. in ...	1986	3019232
establishment of a mouse model for human rhinovirus infection.	we describe here a mouse model for rhinovirus infection using a variant of human rhinovirus type 2 (hrv2/h) which replicated 50- to 300-fold in the lungs of balb/c mice. the variant virus differed only marginally from hrv2/h according to various biochemical parameters. use of a photosensitive inoculum and pretreatment of the animals with actinomycin d were necessary for detection of reproducible and significant levels of virus replication. this mouse model of rhinovirus infection is the first ex ...	1986	3023527
use of monoclonal antibodies to identify four neutralization immunogens on a common cold picornavirus, human rhinovirus 14.	a collection of 35 mouse monoclonal antibodies, raised against human rhinovirus 14 (hrv-14), was used to isolate 62 neutralization-resistant mutants. when cross-tested against the antibodies in a neutralization assay, the mutants fell into four antigenic groups, here called neutralization immunogens: nim-ia, -ib, -ii, and -iii. sequencing the mutant rna in segments corresponding to serotype-variable regions revealed that the amino acid substitutions segregated into clusters, which correlated exa ...	1986	2416951
a neutralizing epitope on human rhinovirus type 2 includes amino acid residues between 153 and 164 of virus capsid protein vp2.	use has been made of a monoclonal antibody (designated 8f5) to map a neutralizing epitope on the viral capsid protein vp2 of human rhinovirus 2 (hrv2). this antibody which was raised against the native virus, neutralizes hrv2 and is also capable of recognizing denatured vp2 on western blots. to examine the binding site of 8f5, vp2 of hrv2 was expressed in escherichia coli. deletions starting at the 3' end were then introduced into the gene for vp2 using bal-31 nuclease. polypeptides shortened at ...	1987	2434607
different rhinovirus serotypes neutralized by antipeptide antibodies.	recently, rossman et al. have described the three-dimensional structure of a human rhinovirus. a possible host cell surface receptor binding site was identified with a cleft on each icosahedral face. two highly conserved amino-acid sequences found in rhino-, polio-, and foot-and-mouth disease (fmd) viruses are located near the base of this site and could be important in maintaining its topology. we have prepared site-specific antibodies to two synthetic peptides which include these sequences. th ...	1987	2444889
virus receptors on lymphoid cells.	the studies described above indicate the advances made in the isolation and characterization of virus receptors of lymphoreticular cells (table i). although the examples of lymphotropic virus receptors cited in this chapter indicate that single membrane glycoproteins can serve as receptors, other nonlymphoid viruses such as vesicular stomatitis virus (vsv) (table i) appear to utilize glycolipid or phospholipid components for cell attachment. these molecules may be responsible for the broad speci ...	1987	2828828
a synthetic peptide which elicits neutralizing antibody against human rhinovirus type 2.	synthetic peptides corresponding to six predicted immunogenic sites on human rhinovirus type 2 (hrv2) have been tested for their reactivity with an anti-virion antibody and for their ability to elicit neutralizing antibody. four of the peptides reacted with hrv2 antiserum in an indirect elisa. rabbit antisera produced to three of these four peptides, one each from vp1, vp2 and vp3, reacted with the virus in an indirect elisa and with the corresponding proteins by western blotting. furthermore, a ...	1987	2822846
direct detection of rhinoviruses by an enzyme-linked immunosorbent assay.	this paper describes the first enzyme-linked immunosorbent assay for the detection of rhinovirus antigens in clinical specimens (nasal washings), either directly or following overnight cell culture amplification. the assay takes approximately 48 hours to perform and utilizes the same rabbit antirhinovirus hyperimmune serum as both the capture and detecting antibody. the latter has been biotin-labelled and is detected via a streptavidin beta-galactosidase preformed complex. this new assay has bee ...	1987	2824684
studies of rhinovirus resistant to an antiviral chalcone.	during studies of the antiviral activity of chalcone ro-09-0410 on human rhinovirus type 9 (rv9) chalcone-resistant strains of rv9 were isolated and appeared with a frequency of about 10(-5) in chalcone sensitive stock. chalcone-dependent viruses were found after further passage. some characteristics of the resistant viruses were studied and compared with those of the wild type virus; a number of differences were detected. they produced smaller plaques and grew to lower titre; they were no longe ...	1987	2825590
survival of human rhinovirus type 14 dried onto nonporous inanimate surfaces: effect of relative humidity and suspending medium.	to study the survival of human rhinovirus 14 on environmental surfaces, each stainless steel disk (1 cm in diameter) was contaminated with 10 microl (about 10(5) plaque-forming units) of the virus suspended in either 1 chi tryptose phosphate broth (tpb), 5 mg/ml of bovine mucin in normal saline, or undiluted human nasal discharge. the inoculum was dried in a laminar flow cabinet for 1 h under ambient conditions. the disks were then placed in a glass chamber (20 +/- 1 degree c) with the relative ...	1987	2825955
cleavage site between vp1 and p2a of human rhinovirus is different in serotypes 2 and 14.	the viral capsid protein vp1 of human rhinovirus serotype 2 (hrv2) was cleaved with cyanogen bromide. the peptides thus obtained were separated on an hplc butyl reversed phase column. their positions on vp1 were determined by amino-terminal sequencing using the known nucleotide sequence of the genomic rna of hrv2. the putative carboxy-terminal peptide was further cleaved with trypsin and the resulting fragments were separated on a c18 reversed phase column. amino-terminus of sequencing of the c- ...	1987	2826658
the atomic structure of mengo virus at 3.0 a resolution.	the structure of mengo virus, a representative member of the cardio picornaviruses, is substantially different from the structures of rhino- and polioviruses. the structure of mengo virus was solved with the use of human rhinovirus 14 as an 8 a resolution structural approximation. phase information was then extended to 3 a resolution by use of the icosahedral symmetry. this procedure gives promise that many other virus structures also can be determined without the use of the isomorphous replacem ...	1987	3026048
structure-activity studies of 5-[[4-(4,5-dihydro-2-oxazolyl) phenoxy]alkyl]-3-methylisoxazoles: inhibitors of picornavirus uncoating.	a series of substituted phenyl analogues of 5-[[4-(4,5-dihydro-2-oxazolyl) phenoxy]alkyl]-3-methylisoxazoles has been synthesized and evaluated in vitro against several human rhinovirus (hrv) serotypes. substituents in the 2-position greatly enhanced activity when compared to the unsubstituted compound. many of these compounds exhibited mean mics (mic) against five serotypes as low as 0.40 microm. the mean mic correlated well (r = 0.83) with the mic80 (the concentration that inhibited 80% of the ...	1987	3027340
effect of reduced endocytosis induced by hypotonic shock and potassium depletion on the infection of hep 2 cells by picornaviruses.	potassium depletion after a brief exposure of the cells to hypotonic medium was used to inhibit endocytosis from coated pits in hep 2 cells. after such treatment the endocytic uptake of transferrin was arrested, and electron microscopy revealed that virtually no coated pits were present at the cell surface, while smooth (uncoated) pits were abundant. under the same conditions the cells were strongly protected against poliovirus, while the cytopathogenic effect of human rhinovirus type 2, hrv 2, ...	1987	3032992
evolutionary relationships within the human rhinovirus genus: comparison of serotypes 89, 2, and 14.	the complete nucleotide sequence of the genome of human rhinovirus type 89 was determined from the cdna that had been cloned into escherichia coli. the genome is 7152 nucleotides long and contains a single large open reading frame of 2164 codons. translation commences at position 619 and ends 42 nucleotides before the poly(a) tract. the positions of three proteolytic cleavage sites in the polyprotein were determined by n-terminal amino acid sequencing of the capsid proteins; the remainder were p ...	1987	3033653
mechanism of entry of human rhinovirus 2 into hela cells.	internalized human rhinovirus 2 (hrv2) undergoes a rapid conformational change leading to recognition by the c-determinant-specific monoclonal antibody 2g2. in the presence of the ionophore monensin, the virus accumulates in the cells in its native conformation and infection is strongly inhibited. at 20 degrees but not at 34 degrees the inhibitory effect of monensin can be overcome by a short incubation of the infected cells at low ph as late as 2 hr after inoculation. incubation of infected cel ...	1987	3033893
the complete nucleotide sequence of coxsackievirus b4 and its comparison to other members of the picornaviridae.	the genome of the prototype stain of coxsackievirus b4 (j.v.b. benschoten) has been cloned in escherichia coli and its complete nucleotide sequence determined. excluding the poly(a) tract, the rna genome is 7395 nucleotides in length and appears to encode a single polyprotein of 2183 amino acids. the predicted amino acid sequence of the polyprotein shows close homology (88%) to that of the previously sequenced coxsackievirus b3 and to certain regions of the polyproteins of the polioviruses and h ...	1987	3037008
monoclonal antibody-aided characterization of cellular p220 in uninfected and poliovirus-infected hela cells: subcellular distribution and identification of conformers.	a monoclonal antibody directed against the mr-220,000 subunit (p220) of the mrna cap-binding complex has been prepared and used to analyze the sucrose gradient sedimentation and subcellular location of p220 and its poliovirus-induced cleavage products. the antibody reacted with p220 on immunoblots of cell lysates from uninfected cells, but only with several smaller polypeptides, the p220 cleavage products, in cell lysates from poliovirus-infected cells. the sedimentation of p220 antigens from un ...	1987	3039164
intranasal chalcone, ro 09-0410, as prophylaxis against rhinovirus infection in human volunteers.	the antirhinovirus agent chalcone ro 09-0410 was tested in double-blind place-controlled volunteer trials for its protective efficacy against experimental rhinovirus infection. fifty volunteers received either drug (26 volunteers) or placebo (24 volunteers) both before and after challenge with 20-40 tissue culture infecting dose (tcid50) of human rhinovirus 2 (rv2). there was no evidence that medication significantly reduced the incidence of infection or illness, indeed there was some increase i ...	1987	3326874
prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges.	following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. in the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a ha ...	1987	3440773
failure of intranasally administered 4', 6-dichloroflavan to protect against rhinovirus infection in man.	4',6-dichloroflavan, a potent inhibitor of rhinovirus replication in tissue culture systems was tested in a double-blind, placebo-controlled volunteer trial for its protective efficacy against experimental rhinovirus infection. dichloroflavan was administered intranasally as a 5 per cent w/v aqueous suspension (40 mg; 5 times per day) for 5 doses before and 21 doses after intranasal challenge with rhinovirus type 9, a virus type known to be highly sensitive to the drug when tested in tissue cult ...	1987	3545152
the molecular biology of human rhinoviruses.	a brief review of recent advances in the understanding of human rhinovirus molecular biology is presented. the importance of recent findings on the elucidation of serotypic diversity and their implications for the viral host-cell receptor site are emphasized. an introduction to the genome structure and to the pathway of gene expression in rhinoviruses leads on to a discussion of the crystal structure of human rhinovirus 14 (hrv14) and the antibody-inducing regions on the surface of the capsid. e ...	1987	2847742
a 'new' generation of more potent synthetic antirhinovirus compounds: comparison of their mics and their synergistic interactions.	a 'new' generation of synthetic antirhinovirus compounds has recently become available for in vitro evaluation. thus a new group of compounds from janssen was found to be 10-fold more active than enviroxime or 57-fold more active than dichloroflavan (dcf), against human rhinovirus 9 (hrv-9). in addition, they were also some 5- and 10-fold more potent than enviroxime and dcf, respectively, against hrv-2. similarly, a 'new' series of antirhinovirus compounds from roche, although as active as envir ...	1987	2833156
comparison of the three-dimensional structure of two human rhinoviruses (hrv2 and hrv14).	an attempt has been made to build a model of human rhinovirus 2 (hrv2) based on the known human rhinovirus 14 (hrv14) structure. hrv2 was selected because its amino acid sequence is known and because it belongs to the minor rhinovirus receptor class as compared to hrv14, which belongs to the major class. initial alignment of hrv2 with hrv14 based on the primary sequence and the knowledge of the three-dimensional structure of hrv14 showed that the most probable position of the majority of inserti ...	1987	2834716
prediction of secondary structure, spatial organization and distribution of antigenic determinants for hepatitis a virus proteins.	on the basis of the secondary structure calculations from the known amino acid sequence we came to the conclusion that hepatitis a virus capsid proteins have the typical antiparallel beta-sheet bilayer structure. the predicted secondary structure of the hav proteins can be well aligned with those of the poliovirus (type 1 mahoney) and human rhinovirus (type 14). it enabled us to use the x-ray structure of the pv-1m and hrv-14 proteins as a template and then, firstly, to localize the positions of ...	1987	2482756
structural analysis of a series of antiviral agents complexed with human rhinovirus 14.	the binding to human rhinovirus 14 of a series of eight antiviral agents that inhibit picornaviral uncoating after entry into host cells has been characterized crystallographically. all of these bind into the same hydrophobic pocket within the viral protein vp1 beta-barrel structure, although the orientation and position of each compound within the pocket was found to differ. the compounds cause the protein shell to be less flexible, thereby inhibiting disassembly. although the antiviral potency ...	1988	2835768
conservation of the putative receptor attachment site in picornaviruses.	a deep canyon or pit on the surfaces of human rhinovirus 14 and mengo virus, respectively, has been proposed as a putative receptor binding site. amino acids lining the surface of the canyon or pit have been identified and show greater conservation than other surface residues.	1988	2835857
evidence for the direct involvement of the rhinovirus canyon in receptor binding.	evidence is presented that indicates a deep crevice located on the surface of human rhinovirus type 14 is involved in virion attachment to cellular receptors. by using mutagenesis of an infectious cdna clone, 11 mutants were created by single amino acid substitutions or insertions at positions 103, 155, 220, 223, and 273 of the structural protein vp1. seven of the recovered mutants had a small plaque phenotype and exhibited binding affinities significantly lower than wild-type virus. one mutant, ...	1988	2840661
detection of the human rhinovirus minor group receptor on renaturing western blots.	the human rhinovirus minor group receptor was extracted from hela cell membranes and partially purified. receptor activity was detected on western blots by binding of 35s-labelled human rhinovirus serotype 2 to the immobilized protein at a position corresponding to an mr of 120 x 10(3).	1988	2844972
evaluation of an enzyme-linked immunosorbent assay that measures rhinovirus-specific antibodies in human sera and nasal secretions.	rhinovirus-specific antibodies have traditionally been detected by their ability to neutralise the homologous rhinovirus serotype in tissue culture. recently, however, we have described an enzyme-linked immunosorbent assay that detects rhinovirus-specific antibodies in sera and nasal secretions [barclay and al-nakib, 1987]. here we describe an evaluation of the elisa in a study involving 71 adult volunteers inoculated intranasally with human rhinovirus type 2 (hrv-2). pre- and post-inoculation s ...	1988	2844987
prediction of three-dimensional models for foot-and-mouth disease virus and hepatitis a virus.	atomic models of foot-and-mouth disease virus and hepatitis a virus have been predicted using amino acid sequence alignments with the known structures of mengo virus and human rhinovirus 14. the structural models are consistent with results of biochemical and immunological studies. the two viruses appear to have surface features exceedingly different than those of other picornaviruses. they also have large hydrophobic cavities within vp1 suggesting that it may be possible to inhibit their infect ...	1988	2845659
modification of experimental rhinovirus colds by receptor blockade.	human rhinovirus (hrv) infection can be inhibited in vitro by antibody directed against the cellular receptor for the major hrv group representing 90% of serotypes. we assessed the prophylactic effectiveness and safety of intranasally administered rhinovirus receptor murine monoclonal antibody (rrma) in two double-blind, place-controlled, randomized studies of volunteers experimentally inoculated with hrv-39. in the first study, rrma administration (135 micrograms/subject in 9 applications, -17 ...	1988	2849376
human rhinovirus 3c protease: cloning and expression of an active form in escherichia coli.	a cdna encoding the viral protease from the 3c region of human rhinovirus type 14 was expressed in escherichia coli through the use of a periplasmic secretion vector. the recombinant protease contained an eight amino acid n-terminal extension that enabled its detection by a specific antibody. it was expressed at a level of approximately 1 mg/l of e. coli culture. biological activity of the protease was assessed in vitro by using a chemically synthesized peptide consisting of a consensus picornav ...	1988	2851319
effect of isoflavans and isoflavenes on rhinovirus 1b and its replication in hela cells.	the effect of newly synthesized halogenated isoflavans and isoflavenes on human rhinovirus 1b (hrv 1b) infection of hela cells has been examined. both series of drugs inhibited virus plaque formation in cell cultures, isoflavans being more effective than isoflavenes. cells pretreated with compounds before challenge with hrv 1b became resistant to the virus-induced cytopathic effect. the antiviral state induced by the most active compounds persisted for at least 10 h and did not appear to be medi ...	1988	2852916
expression and processing of human rhinovirus type 14 polypeptide precursors in escherichia coli maxicells.	human rhinovirus serotype-14 (hrv-14) cdna, encompassing 87.9% of the coding region, was subcloned in an escherichia coli expression vector, generating plasmid pkcc101. hrv-14 polypeptides encoded by pkcc101 were synthesized in e. coli maxicells. pulse-chase experiments with pkcc110, a smaller derivative of pkcc101 containing the protease 3c coding region, have clearly demonstrated the proteolysis of a 55-kda precursor to several polypeptides, including a doublet with the expected size of protea ...	1988	2853102
the use of molecular-replacement phases for the refinement of the human rhinovirus 14 structure.	the structure of human rhinovirus 14 has been refined, by the method of restrained least squares, to an r factor of 0.16 for various random samples between 6 and 3 a resolution with f greater than 3 sigma (f). as a first step the non-crystallographic symmetry parameters were optimized using the initial atomic model in a rigid-body refinement procedure. phase determination by the molecular-replacement phase extension and refinement procedure was continued to 2.94 a resolution, employing the impro ...	1988	2856083
the nucleotide sequence of human rhinovirus 1b: molecular relationships within the rhinovirus genus.	we have determined the complete nucleotide sequence of human rhinovirus 1b and made comparisons with other rhinoviruses. extensive homology was found with serotypes 2 and 89 but the similarity to serotype 14 was considerably less. rhinovirus-specific characteristics have been noted, in particular the length of the 5' non-coding region and the pattern of codon usage, and these may be sufficient to define the rhinoviruses as a distinct genus rather than being considered as members of the enterovir ...	1988	2826669
enantiomeric effects of homologues of disoxaril on the inhibitory activity against human rhinovirus-14.	x-ray crystallography studies of racemic 5-[7-[4-(4,5-dihydro-4-methyl-2-oxazolyl)phenoxy]heptyl]- 3-methylisoxazole bound to human rhinovirus-14 (hrv-14) indicate selective binding of the s isomer. this result correlates well with the 10-fold greater activity of the s isomer as compared to the r isomer. the enantiomeric effect on activity is explained by a hydrophobic interaction of the methyl group in the case of 2a, with a pocket formed by leu106 and ser107. the 4-ethyl, 4-propyl, and 4-butyl ...	1988	2831362
characteristics of the minor group receptor of human rhinoviruses.	the receptor for the minor group of human rhinoviruses was solubilized from hela cell membranes with various detergents. virus binding activity was determined in a filter binding assay using 35s-labeled human rhinovirus 2 (hrv2) as a probe. the receptor protein was enriched on lens culinaris lectin columns and the active fractions were further purified by gel permeation and anion exchange chromatography. the receptor has an apparent molecular weight of 450 kda in the presence of detergent. the b ...	1988	2831654
use of crna probes for the detection of enteroviruses by molecular hybridization.	subgenomic fragments of cdna from poliovirus type 1 were inserted downstream from the sp6 or the t7 promoter in a gemini riboprobe vector and their in vitro synthesized rna transcripts were used as radiolabeled probes for the detection of enteroviral rnas by molecular hybridization. the crna transcripts appeared to be more sensitive probes than the corresponding cdnas. in vitro transcripts of the 5' noncoding region (5' nc riboprobe) were able to detect all of 14 reference enterovirus strains te ...	1988	2448419
antigenic sites on foot-and-mouth disease virus type a10.	a set of monoclonal antibodies was used to isolate nonneutralizable foot-and-mouth disease virus variants, and the rnas of the variants were sequenced. cross-neutralization studies and mapping of the amino acid changes indicated two major antigenic sites. the first site was trypsin sensitive and included the vp1 140 to 160 sequence. the second site was trypsin insensitive and included mainly vp3 residues. two minor sites were located near vp1 169 and on the c terminus of vp1. comparison with pol ...	1988	2455819
identification of an immunodominant antigenic site involving the capsid protein vp3 of hepatitis a virus.	hepatitis a virus, an hepatotropic picornavirus, is a common cause of acute hepatitis in man for which there is no available vaccine. competitive binding studies carried out in solid phase suggest that neutralizing monoclonal antibodies to hepatitis a virus recognize a limited number of epitopes on the capsid surface, although the polypeptide locations of these epitopes are not well defined. neutralization-escape mutants, selected for resistance to monoclonal antibodies, demonstrate broad cross- ...	1988	2460866
n-agib of poliovirus type 1: a discontinuous epitope formed by two loops of vp1 comprising residues 96-104 and 141-152.	analysis of resistant mutants to neutralizing monoclonal antibodies revealed a discontinuous neutralization epitope on vp1 of poliovirus type 1, mahoney. the epitope has the unique property of being also part of a sequential epitope within neutralization antigenic site i (n-agi). it is formed by residues in the loop 96-104 connecting the b and c strand and in the loop 141-152 connecting the d and e strand of vp1. because of strong analogy to neutralization immunogen ib (nimib) of human rhinoviru ...	1989	2471354
infective respiratory exacerbations in young adults with cystic fibrosis: role of viruses and atypical microorganisms.	thirty six adults with cystic fibrosis were studied over one year to determine the incidence of infection with respiratory viruses and atypical organisms. nineteen patients entered the study during an acute exacerbation of respiratory symptoms with an increase in purulent sputum production, cough, or breathlessness accompanied by a fall in fev1 (group 1); 17 patients entered when they were stable both clinically and in terms of lung function values (group 2). group 1 patients had a mean of 2.6 ( ...	1989	2588211
the canyon hypothesis. hiding the host cell receptor attachment site on a viral surface from immune surveillance.	the three-dimensional structure of human rhinovirus 14 has a deep surface depression or "canyon" encircling each of the twelve 5-fold vertices. the canyon's surface is inaccessible to the broad antigen binding region of antibodies, permitting conservation of residues that might be required for host cell receptor recognition without danger of attack by the host's immune system. in contrast, the exposed surface features, where neutralizing antibodies are known to bind, change rapidly under pressur ...	1989	2670920