Publications
| Title | Abstract | Year Filter | PMID(sorted ascending) Filter |
|---|
| 2a proteinase of human rhinovirus cleaves cytokeratin 8 in infected hela cells. | rhino- and enteroviruses encode two proteinases, 2a and 3c, which are responsible for the processing of the viral polyprotein and for cleavage of several cellular proteins. to identify further targets of the 2a proteinase of human rhinovirus serotype 2 (hrv2), an in vitro cleavage assay followed by two-dimensional electrophoresis was employed. cytokeratin 8, a member of the intermediate filament group of proteins, was found to be proteolytically cleaved in vitro by the 2a proteinase of hrv2 and ... | 2000 | 10867028 |
| structure of human rhinovirus serotype 2 (hrv2). | human rhinoviruses are classified into a major and a minor group based on their binding to icam-1 or to members of the ldl-receptor family, respectively. they can also be divided into groups a and b, according to their sensitivity towards a panel of antiviral compounds. the structure of human rhinovirus 2 (hrv2), which uses the ldl receptor for cell attachment and is included in antiviral group b, has been solved and refined at 2.6 a resolution by x-ray crystallography to gain information on the ... | 2000 | 10903863 |
| respiratory infections and asthma. | clinical and experimental evidence suggests an important role for respiratory infections in the development of asthma attacks. viral upper respiratory infections have been associated with 80% of asthma exacerbations in children and 50% of all asthma episodes in adults. human rhinovirus has been implicated as the principal virus associated with asthma episodes. separate studies indicate that atypical bacteria such as chlamydia pneumoniae and mycoplasma pneumoniae may precipitate asthma symptoms. ... | 2000 | 10919505 |
| a novel method of aligning molecules by local surface shape similarity. | a novel shape-based method has been developed for overlaying a series of molecule surfaces into a common reference frame. the surfaces are represented by a set of circular patches of approximately constant curvature. two molecules are overlaid using a clique-detection algorithm to find a set of patches in the two surfaces that correspond, and overlaying the molecules so that the similar patches on the two surfaces are coincident. the method is thus able to detect areas of local, rather than glob ... | 2000 | 10921773 |
| expression of intercellular adhesion molecule-1 (icam-1) in nasal epithelial cells of atopic subjects: a mechanism for increased rhinovirus infection? | since clinical experimental studies indicate that upper respiratory tract viral infections may exacerbate acute asthma symptoms in atopic/asthmatic individuals, we have investigated the expression and modulation of icam-1 on human nasal epithelial cells (hnec) from normal and atopic subjects. icam-1 is the attachment molecule for the majority of serotypes of human rhinovirus (hrv), including hrv-14, and is also critical for the migration and activation of immune effector cells. basal icam-1 expr ... | 2000 | 10931151 |
| in vitro activity of pleconaril and ag7088 against selected serotypes and clinical isolates of human rhinoviruses. | background: we tested the in vitro activity of pleconaril and ag7088 against five numbered human rhinovirus (hrv) serotypes and 46 clinical hrv isolates of undefined serotype recovered from patients with common colds. antiviral effect of pleconaril and ag7088 were assessed by cytophathic effect (cpe) inhibition assays in ohio helai cells using microscopic and spectrophotometric methods. both compounds were tested at concentrations of 1.0, 0.1 and 0.01 microg/ml. for the numbered hrv serotypes, t ... | 2000 | 10974374 |
| role of nf-kappa b in cytokine production induced from human airway epithelial cells by rhinovirus infection. | infection of human epithelial cells with human rhinovirus (hrv)-16 induces rapid production of several proinflammatory cytokines, including il-8, il-6, and gm-csf. we evaluated the role of nf-kappab in hrv-16-induced il-8 and il-6 production by emsa using oligonucleotides corresponding to the binding sites for nf-kappab in the il-6 and il-8 gene promoters. consistent with the rapid induction of mrna for il-8 and il-6, maximal nf-kappab binding to both oligonucleotides was detected at 30 min afte ... | 2000 | 10975857 |
| [the pathogenesis and therapy of virus infection-induced senile bronchial asthma]. | we investigated the pathogenesis and therapy of virus infection-induced senile bronchial asthma in vitro. to examine the effects of rhinovirus infection on the production of cytokines and intercellular adhesion molecule-1 (icam-1), human tracheal epithelial cells and submucosal gland cells were cultured, and infected with human rhinovirus. rhinovirus upregulated the production of interleukin (il)-1 beta, il-6, il-8, tumor necrosis factor (tnf)-alpha in supernatants of epithelial cells and submuc ... | 2000 | 10998927 |
| s-nitrosothiols as novel, reversible inhibitors of human rhinovirus 3c protease. | human rhinovirus (hrv) 3c protease was inactivated by a series of s-nitrosothiols. these compounds exhibited different inhibitory activities in a time- and concentration-dependent manner with second-order rate constants (kinact/k(i)) ranging from 131 to 5360 m(-1) min(-1). the inactive enzyme could be re-activated by dtt, gsh and ascorbate, which indicated the inactivation mechanism was through an s-transnitrosylation process. | 2000 | 10999479 |
| affinity capillary electrophoresis for the assessment of complex formation between viruses and monoclonal antibodies. | the formation of complexes of human rhinovirus (serotype hrv2 and hrv14) with nonaggregating neutralizing monoclonal antibodies was investigated by affinity capillary electrophoresis. the method is based on preincubation of virus with antibody, followed by ce analysis. at low antibody-to-virus ratios, peaks corresponding to the complexes were broad, pointing to the presence of a heterogeneous population of virions with various numbers of antibodies bound; at a high molar ratio between virus and ... | 2000 | 11028622 |
| extremely efficient cleavage of eif4g by picornaviral proteinases l and 2a in vitro. | certain picornaviruses encode proteinases which cleave the translation initiation factor eif4g, a member of the eif4f complex which recruits mrna to the 40s ribosomal subunit during initiation of protein synthesis in eukaryotes. we have compared the efficiency of eif4g cleavage in rabbit reticulocyte lysates during translation of mrnas encoding the foot-and-mouth disease virus leader proteinase (lpro) or the human rhinovirus 2apro. under standard translation conditions, lpro cleaved 50% of eif4g ... | 2000 | 11034318 |
| role of p38 mitogen-activated protein kinase in rhinovirus-induced cytokine production by bronchial epithelial cells. | the stress-activated protein kinase p38 plays a central role in the regulation of cytokine biosynthesis by various cell types in response to a wide range of stimuli. because the local inflammatory response and the infiltration of neutrophils is thought to contribute to the symptoms and sequelae of rhinovirus infection, we investigated the role of p38 kinase in cytokine and chemokine elaboration in airway epithelial cells infected with human rhinovirus. rhinovirus-39 infection of beas-2b cells re ... | 2000 | 11046054 |
| vldl receptor fragments of different lengths bind to human rhinovirus hrv2 with different stoichiometry. an analysis of virus-receptor complexes by capillary electrophoresis. | the formation of complexes between the minor receptor group human rhinovirus hrv2 and two recombinant soluble receptor fragments derived from the human very low density lipoprotein receptor (vldlr) and containing ligand-binding repeats 1-3 (mbp.vldlr(1-3)) or 1-8 (mbp.vldlr(1-8)) fused to the carboxyl terminus of the maltose-binding protein was analyzed by affinity capillary electrophoresis. at low molar ratios of receptor/virus, the peaks corresponding to substoichiometric complexes were broad ... | 2001 | 11054420 |
| inhibition of clathrin-dependent endocytosis has multiple effects on human rhinovirus serotype 2 cell entry. | minor group human rhinoviruses (exemplified by human rhinovirus serotype 2 (hrv2)) use members of the low density lipoprotein receptor family for cell entry; all these receptors possess clathrin-coated pit localization signals. viral infection should thus be inhibited under conditions of impaired clathrin-mediated endocytosis. however, madshus et al. reported an increase in the cytopathic effect of hrv2 infection in hep-2 cells upon suppression of clathrin-dependent endocytosis by hypotonic shoc ... | 2001 | 11073943 |
| translation and replication of human rhinovirus type 14 and mengovirus in xenopus oocytes. | we have previously shown that xenopus oocytes require coinjection of both poliovirus rna and hela cell extracts to support a complete cycle of viral replication yielding high levels of infectious viral particles. this novel system provides a tool for identifying host factors and for biochemically dissect individual steps that lead to virus production. here we demonstrate that xenopus oocytes are able to support replication of other picornaviruses such as human rhinovirus 14 and mengovirus. unlik ... | 2000 | 11090201 |
| the cellular receptor to human rhinovirus 2 binds around the 5-fold axis and not in the canyon: a structural view. | human rhinovirus serotype 2 (hrv2) belongs to the minor group of hrvs that bind to members of the ldl-receptor family including the very low density lipoprotein (vldl)-receptor (vldl-r). we have determined the structures of the complex between hrv2 and soluble fragments of the vldl-r to 15 a resolution by cryo-electron microscopy. the receptor fragments, which include the first three ligand-binding repeats of the vldl-r (v1-3), bind to the small star-shaped dome on the icosahedral 5-fold axis. t ... | 2000 | 11101504 |
| detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease. | common colds are associated with exacerbations of chronic obstructive pulmonary disease (copd). however, the role of the common cold virus (human rhinovirus) in the production of symptoms and lower airway inflammation at copd exacerbation is unknown. thirty three patients with moderate-to-severe copd were seen at baseline, when the number of chest infections in the previous year was noted, and acutely at copd exacerbation. within 48 h after the onset of the exacerbation and at baseline, nasal as ... | 2000 | 11106212 |
| complete nucleotide sequence of the chiba virus genome and functional expression of the 3c-like protease in escherichia coli. | we cloned the genome rna of the chiba virus (chv; hu/nlv/chiba 407/1987/jp) and determined its complete nucleotide sequence. the genome is predicted to be a positive-sense, single-stranded rna of 7697 bases, excluding a poly(a) tract. comparison of the nucleotide and amino acid sequences with those of other members of the species norwalk virus (nv) revealed that chv belongs to genogroup i nv. the chv genome contains three open reading frames (orfs). a large 5'-terminal orf (orf1) encodes a polyp ... | 2000 | 11118371 |
| expression and folding of human very-low-density lipoprotein receptor fragments: neutralization capacity toward human rhinovirus hrv2. | minor group human rhinoviruses (hrvs) use members of the low-density lipoprotein receptor family for cell entry. to investigate the utility of receptor fragments as viral inhibitors, various polypeptide segments derived from the ligand binding domain of human very-low-density lipoprotein receptor (vldlr) were expressed in a soluble form in bacteria. whereas none of the fragments was active in virus binding immediately after recovery from the cell lysates, constructs encompassing complement type ... | 2000 | 11118376 |
| sputum and plasma endothelin-1 levels in exacerbations of chronic obstructive pulmonary disease. | endothelin (et)-l is a bronchoconstrictor peptide produced in the airways. it has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role in exacerbations of chronic obstructive pulmonary disease (copd). | 2001 | 11120901 |
| type 2 rhinovirus infection of cultured human tracheal epithelial cells: role of ldl receptor. | to examine the role of the low-density lipoprotein (ldl) receptor on minor group human rhinovirus (rv) infection, primary cultures of human tracheal epithelial cells were infected with a minor group (rv2) or a major group (rv14) rv. viral infection was confirmed by showing with pcr that viral titers in supernatants and lysates from infected cells increased with time. rv2 and rv14 increased expression of mrna and protein of the ldl receptor on the cells and the cytokine production. rv2 induced ac ... | 2001 | 11159023 |
| molecular dynamics simulations of human rhinovirus and an antiviral compound. | the human rhinovirus 14 (hrv14) protomer, with or without the antiviral compound win 52084s, was simulated using molecular dynamics and rotational symmetry boundary conditions to model the effect of the entire icosahedral capsid. the protein asymmetrical unit, comprising four capsid proteins (vp1, vp2, vp3, and vp4) and two calcium ions, was solvated both on the exterior and the interior to fill the inside of the capsid. the stability of the simulations of this large system (~800 residues and 6, ... | 2001 | 11159387 |
| the c-terminal residues of poliovirus proteinase 2a(pro) are critical for viral rna replication but not for cis- or trans-proteolytic cleavage. | poliovirus proteinase 2a(pro) is an essential enzyme involved in cleavages of viral and cellular proteins during the infectious cycle. evidence has been obtained that 2a(pro) is also involved in genome replication. all enteroviruses have a negatively charged cluster of amino acids at their c terminus (e(e)/(d)(e)/(d)ameq-nh(2)), a common motif suggesting function. when aligned with enterovirus sequences, the 2a(pro) proteinase of human rhinovirus type 2 (hrv2) has a shorter c terminus (ee.q:-nh( ... | 2001 | 11161279 |
| activation of human rhinovirus-14 3c protease. | the catalytic efficiency of human rhinovirus-14 (hrv14) 3c protease as a function of solvents and other regulators has been investigated using synthetic peptides as substrates. the proteolytic activity of hrv14 3c was found to be strongly stimulated by a series of anions in vitro and the activation was accompanied by changed km, kcat, and increased kcat/km values. a more than 72-fold increase in the 3c catalytic efficiency toward peptide substrates was observed in the presence of 0.8 m sodium su ... | 2001 | 11162821 |
| influenza virus and rhinovirus-related otitis media: potential for antiviral intervention. | adults frequently develop eustachian tube dysfunction and middle ear pressure (mep) abnormalities during natural and experimental influenza and human rhinovirus (hrv) infections. oral rimantadine treatment did not reduce the otologic manifestations of experimental influenza in adults or natural influenza in children. however, intranasal zanamivir and oral oseltamivir significantly reduced mep abnormalities during experimental influenza in adults, and oseltamivir treatment appears to reduce the l ... | 2000 | 11163466 |
| rhinovirus infection induces expression of type 2 nitric oxide synthase in human respiratory epithelial cells in vitro and in vivo. | human rhinovirus (hrv) infections are the predominant cause of the common cold and are associated with exacerbations of asthma. nitric oxide (no) may play an important role in host defense by means of its potent antiviral properties. | 2001 | 11174188 |
| viral capsid mobility: a dynamic conduit for inactivation. | mass spectrometry and fluorescent probes have provided direct evidence that alkylating agents permeate the protein capsid of naked viruses and chemically inactivate the nucleic acid. n-acetyl-aziridine and a fluorescent alkylating agent, dansyl sulfonate aziridine, inactivated three different viruses, flock house virus, human rhinovirus-14, and foot and mouth disease virus. mass spectral studies as well as fluorescent probes showed that alkylation of the genome was the mechanism of inactivation. ... | 2001 | 11226229 |
| synthesis and anti-rhinovirus activity of 2-styrylchromones. | 2-styrylchromones were synthesized as vinylogues of 2-phenylchromones (flavones), a broad class of anti-rhinovirus compounds. the antiviral activity of 2-styrylchromones and 3-hydroxy-1-(2-hydroxyphenyl)-5-phenyl-2,4-pentadien-1-ones, which are intermediates in the synthesis, was evaluated against two selected serotypes of human rhinovirus, 1b and 14, by a plaque reduction assay in hela cell cultures. all of the compounds interfered with hrv 1b replication, with the exception of 3-hydroxy-1-(2-h ... | 2000 | 11227995 |
| nitric oxide inhibits rhinovirus-induced granulocyte macrophage colony-stimulating factor production in bronchial epithelial cells. | infection of asthmatics with human rhinovirus (hrv) enhances airway eosinophilia and airways hyperreactivity. the current studies were performed to further characterize hrv-induced generation by human bronchial epithelial cells of granulocyte macrophage colony-stimulating factor (gm-csf), a cytokine that could contribute to airway eosinophilia by increasing the survival and activation of eosinophils, and to determine the effects of the antiviral agent nitric oxide (no) on hrv-induced gm-csf prod ... | 2001 | 11245631 |
| ag-7088 pfizer. | pfizer (formerly agouron) is developing ag-7088, a peptide aldehyde that targets the human rhinovirus (hrv) 3c proteinase enzyme and has potential for the treatment of the common cold. a phase ii efficacy study has been completed in healthy patients infected with the virus [318668] and in november 1999, agouron initiated a large, double-blind, placebo-controlled trial in the us, in individuals within 36 h of experiencing cold symptoms [346362]. ag-7088 is derived from ag-6084, the development of ... | 2000 | 11249711 |
| clinical features of patients with acute respiratory illness and rhinovirus in their bronchoalveolar lavages. | several reports in selected populations suggest that human rhinovirus (hrv) may be responsible for lower respiratory tract infections or pneumonia. we describe clinical features of all patients with rhinovirus cultured from their bronchoalveolar lavage (bal) during a 10-yr period in a tertiary care center. | 2001 | 11255093 |
| disruption of the interaction of mammalian protein synthesis eukaryotic initiation factor 4b with the poly(a)-binding protein by caspase- and viral protease-mediated cleavages. | eukaryotic initiation factor (eif) 4b interacts with several components of the initiation pathway and is targeted for cleavage during apoptosis. in a cell-free system, cleavage of eif4b by caspase-3 coincides with a general inhibition of protein synthetic activity. affinity chromatography demonstrates that mammalian eif4b interacts with the poly(a)-binding protein and that a region consisting of the n-terminal 80 amino acids of eif4b is both necessary and sufficient for such binding. this intera ... | 2001 | 11274152 |
| membrane-associated respiratory syncytial virus f protein expressed from a human rhinovirus type 14 vector is immunogenic. | human rhinovirus (hrv) replicons have the potential to serve as respiratory vaccine vectors for mucosal immunization in humans. however, since many vaccine immunogens of interest are glycosylated, an important concern is whether hrv replicons are capable of expressing glycosylated proteins. the human respiratory syncytial virus (rsv) fusion (f) protein was chosen as a model glycoprotein and the hrv replicon deltap1fvp3 was generated by inserting the f protein-coding sequence in frame and in lieu ... | 2001 | 11277694 |
| analysis of the aphthovirus 2a/2b polyprotein 'cleavage' mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal 'skip'. | the 2a region of the aphthovirus foot-and-mouth disease virus (fmdv) polyprotein is only 18 aa long. a 'primary' intramolecular polyprotein processing event mediated by 2a occurs at its own c terminus. fmdv 2a activity was studied in artificial polyproteins in which sequences encoding reporter proteins flanked the 2a sequence such that a single, long, open reading frame was created. the self-processing properties of these artificial polyproteins were investigated and the co-translational 'cleava ... | 2001 | 11297676 |
| antiviral activity of an extract derived from roots of eleutherococcus senticosus. | a liquid extract from eleutherococcus senticosus roots inhibited the productive replication of human rhinovirus (hrv), respiratory syncytial virus (rsv) and influenza a virus in cell cultures infected with these viruses, all of which belong to the rna type viruses. analysis of virus production after treatment of the infected cells using plaque-reduction assays showed a strong antiviral activity of the eleutherococcus extract. in contrast, no effect was detected using the same protocol for cells ... | 2001 | 11397509 |
| in vitro antiviral activity of the anthraquinone chrysophanic acid against poliovirus. | chrysophanic acid (1,8-dihydroxy-3-methylanthraquinone), isolated from the australian aboriginal medicinal plant dianella longifolia, has been found to inhibit the replication of poliovirus types 2 and 3 (picornaviridae) in vitro. the compound inhibited poliovirus-induced cytopathic effects in bgm (buffalo green monkey) kidney cells at a 50% effective concentration of 0.21 and 0.02 microgram/ml for poliovirus types 2 and 3, respectively. the compound inhibited an early stage in the viral replica ... | 2001 | 11428243 |
| structure of an rna hairpin from hrv-14. | the 5' noncoding region of the picornaviral genome begins with a cloverleaf which is required for viral replication, due at least in part to an interaction with the viral rna polymerase as part of a fusion with the predominant viral protease. the necessary region of the cloverleaf has previously been narrowed to a highly conserved stem-loop. the solution structure of a 14-nucleotide rna hairpin, which is part of the conserved stem-loop from human rhinovirus isotype 14, is presented here. the sec ... | 2001 | 11434774 |
| effects of tumor necrosis factor-alpha, epidermal growth factor and transforming growth factor-alpha on interleukin-8 production by, and human rhinovirus replication in, bronchial epithelial cells. | previous studies have shown that the epidermal growth factor (egf) and transforming growth factor-alpha (tgf-alpha), members of the egf growth factor family, regulate processes involved in airway repair after injury. our studies were conducted to determine whether egf and tgf-alpha directly control processes involved in the pathogenesis of airway inflammation and/or modulate the inflammatory effects of tnf-alpha in the airway mucosa. we have found that these cell growth factors directly induced ... | 2001 | 11460304 |
| detailed analysis of the requirements of hepatitis a virus internal ribosome entry segment for the eukaryotic initiation factor complex eif4f. | the hepatitis a virus (hav) internal ribosome entry segment (ires) is unique among the picornavirus iress in that it is inactive in the presence of either the entero- and rhinovirus 2a or aphthovirus lb proteinases. since these proteinases both cleave eukaryotic initiation factor 4g (eif4g) and hav ires activity could be rescued in vitro by addition of eif4f to proteinase-treated extracts, it was concluded that the hav ires requires eif4f containing intact eif4g. here, we show that the inability ... | 2001 | 11483730 |
| hbv core particles as a carrier for b cell/t cell epitopes. | in the middle 80s, recombinant hepatitis b virus cores (hbc) gave onset to icosahedral virus-like particles (vlps) as a basic class of non-infectious carriers of foreign immunological epitopes. the recombinant hbc particles were used to display immunodominant epitopes of hepatitis b, c, and e virus, human rhinovirus, papillomavirus, hantavirus, and influenza virus, human and simian immunodeficiency virus, bovine and feline leukemia virus, foot-and-mouth disease virus, murine cytomegalovirus and ... | 2001 | 11509871 |
| viral evolution toward change in receptor usage: adaptation of a major group human rhinovirus to grow in icam-1-negative cells. | major receptor group common cold virus hrv89 was adapted to grow in hep-2 cells, which are permissive for minor group human rhinoviruses (hrvs) but which only marginally support growth of major-group viruses. after 32 blind passages in these cells, each alternating with boosts of the recovered virus in hela cells, hrv89 acquired the capacity to effectively replicate in hep-2 cells, attaining virus titers comparable to those in hela cells although no cytopathic effect was observed. several clones ... | 2001 | 11533194 |
| complexes between monoclonal antibodies and receptor fragments with a common cold virus: determination of stoichiometry by capillary electrophoresis. | complex formation between monoclonal antibodies or soluble receptor fragments and a human rhinovirus is quantified by relating the concentration of the antibody or receptor under equilibrium conditions to the initial concentration of the virus. within a given concentration range of the reactants, the shape of the resulting curve depends only on the value of the dissociation constant of the particular system studied. using antibodies and receptor fragments, cases for high, low, and intermediate a ... | 2001 | 11534714 |
| protease inhibitors as potential antiviral agents for the treatment of picornaviral infections. | the picornavirus family contains several human pathogens including human rhinovirus (hrv) and hepatitis a virus (hav). in the case of hrvs, these small single-stranded positive-sense rna viruses translate their genetic information into a polyprotein precursor which is further processed mainly by two viral proteases designated 2a and 3c. the 2a protease (2apro) makes the first cleavage between the structural and non-structural proteins, while 3c protease (3cpro) catalyzes most of the remaining in ... | 2001 | 11548209 |
| antiviral action of euphorbium compositum and its components. | euphorbium compositum sn (biologische heilmittel heel gmbh, baden-baden, germany, a homeopathic combination preparation available in form of drops, nasal spray, and injection solution), is prescribed for inflammation of the mucosae of the nose and sinuses. infections in these areas are primarily of viral origin although bacterial superinfections are also common. | 2001 | 11574744 |
| design and synthesis of irreversible depsipeptidyl human rhinovirus 3c protease inhibitors. | novel tripeptidyl c-terminal michael acceptors with an ester replacement of the p(2)-p(3) amide bond were investigated as irreversible inhibitors of the human rhinovirus (hrv) 3c protease (3cp). when screened against hrv serotype-14 the best compound was shown to have very good 3cp inhibition (k(obs)/[i]=270,000m(-1)s(-1)) and potent in vitro antiviral activity (ec(50)=7.0nm). | 2001 | 11591501 |
| biochemical and genetic studies of the initiation of human rhinovirus 2 rna replication: purification and enzymatic analysis of the rna-dependent rna polymerase 3d(pol). | the replication of human rhinovirus 2 (hrv2), a positive-stranded rna virus belonging to the picornaviridae, requires a virus-encoded rna polymerase. we have expressed in escherichia coli and purified both a glutathione s-transferase fusion polypeptide and an untagged form of the hrv2 rna polymerase 3d(pol). using in vitro assay systems previously described for poliovirus rna polymerase 3d(pol) (j. b. flanegan and d. baltimore, proc. natl. acad. sci. usa 74:3677-3680, 1977; a. v. paul, j. h. van ... | 2001 | 11602737 |
| biochemical and genetic studies of the initiation of human rhinovirus 2 rna replication: identification of a cis-replicating element in the coding sequence of 2a(pro). | we have previously shown that the rna polymerase 3d(pol) of human rhinovirus 2 (hrv2) catalyzes the covalent linkage of ump to the terminal protein (vpg) using poly(a) as a template (k. gerber, e. wimmer, and a. v. paul, j. virol. 75:10969-10978, 2001). the products of this in vitro reaction are vpgpu, vpgpupu, and vpg-poly(u), the 5' end of minus-strand rna. in the present study we used an assay system developed for poliovirus 3d(pol) (a. v. paul, e. rieder, d. w. kim, j. h. van boom, and e. wi ... | 2001 | 11602738 |
| interaction of picornavirus 2c polypeptide with the viral negative-strand rna. | the picornavirus membrane-associated polypeptide 2c is believed to be required for viral rna synthesis. hepatitis a virus (hav)- and human rhinovirus (hrv)-encoded recombinant 2c proteins have been expressed, purified and examined for their ability to interact with the terminal sequences of viral positive- and negative-strand rnas. the results demonstrate that both the hav- and the hrv-encoded 2c polypeptide specifically interact with the 3'-terminal sequences of the negative-strand rna, but not ... | 2001 | 11602773 |
| involvement of proteasome alpha-subunit psma7 in hepatitis c virus internal ribosome entry site-mediated translation. | ribozymes are small catalytic rna molecules that can be engineered to enzymatically cleave rna transcripts in a sequence-specific fashion and thereby inhibit expression and function of the corresponding gene product. with their simple structures and site-specific cleavage activity, they have been exploited as potential therapeutic agents in a variety of human disorders, including hepatitis c virus (hcv) infection. we have designed a hairpin ribozyme (rz3'x) targeting the hcv minus-strand replica ... | 2001 | 11713272 |
| pharmacokinetics and safety of an antirhinoviral agent, ruprintrivir, in healthy volunteers. | a single-dose study and a multiple-dose study of the safety and pharmacokinetics of ruprintrivir, a new selective irreversible inhibitor of human rhinovirus 3c protease, were conducted with healthy adult volunteers. both studies were double-blind, randomized, placebo-controlled, parallel-group investigations of ruprintrivir administered intranasally at two dose levels. the parent drug and its acid metabolite, ag7185, were measured in plasma samples and nasal washings, and the safety of the treat ... | 2002 | 11796347 |
| genetic clustering of all 102 human rhinovirus prototype strains: serotype 87 is close to human enterovirus 70. | human rhinoviruses (hrv), common agents of respiratory infections, comprise 102 designated serotypes. the genetic relationships of hrv prototype strains and the possibility of using genetic identification of a given hrv field strain were studied. genomic sequences in the vp4/vp2 region were obtained from all 102 prototype strains. phylogenetic analysis included 61 recently isolated finnish field strains. seventy-six out of the 102 prototype strains clustered in the hrv genetic group a and 25 in ... | 2002 | 11807226 |
| structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3c protease inhibitors. part 7: structure-activity studies of bicyclic 2-pyridone-containing peptidomimetics. | the structure-based design, chemical synthesis, and biological evaluation of bicyclic 2-pyridone-containing human rhinovirus (hrv) 3c protease (3cp) inhibitors are described. an optimized compound is shown to exhibit antiviral activity when tested against a variety of hrv serotypes (ec(50)'s ranging from 0.037 to 0.162 microm). | 2002 | 11858991 |
| rhinovirus infection increases 5-lipoxygenase and cyclooxygenase-2 in bronchial biopsy specimens from nonatopic subjects. | rhinovirus infections cause wheeze, cough, and bronchial hyperresponsiveness. to investigate the involvement of cysteinyl-leukotrienes and prostanoids in these symptoms, bronchial biopsy specimens from 9 normal subjects (nonatopic and with no history of chronic lung disease) were immunostained for 5-lipoxygenase (5-lo) and cyclooxygenase (cox) pathway enzymes 2 weeks before and 4 days after experimental infection with human rhinovirus serotype 16. 5-lo-positive cell counts increased 9-fold (from ... | 2002 | 11865407 |
| peptidyl diazomethyl ketones inhibit the human rhinovirus 3c protease: effect on virus yield by partial block of p3 polyprotein processing. | the efficacy of a series of diazomethyl ketones (dmks) was measured in rhinovirus-infected cultures and against the hrv14 3c protease. their specificity and potency were confirmed against purified recombinant enzyme expressed in a yeast secretion system. an internally quenched fluorescent peptide substrate was used to assess the potency against the enzyme, obtaining a 50% inhibitory concentration (ic50) of 1 microm for both z-l-f-q-chn2 and z-v-l-f-q-chn2, while a lower affinity was observed for ... | 2001 | 11900346 |
| determinants of the recognition of enteroviral cloverleaf rna by coxsackievirus b3 proteinase 3c. | the initiation of enteroviral positive-strand rna synthesis requires the presence of a functional ribonucleoprotein complex containing a cloverleaf-like rna secondary structure at the 5' end of the viral genome. other components of the ribonucleoprotein complex are the viral 3cd proteinase (the precursor protein of the 3c proteinase and the 3d polymerase), the viral 3ab protein and the cellular poly(rc)-binding protein 2. for a molecular characterization of the rna-binding properties of the ente ... | 2002 | 11911365 |
| structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3c protease inhibitors. 6. structure-activity studies of orally bioavailable, 2-pyridone-containing peptidomimetics. | the structure-based design, chemical synthesis, and biological evaluation of various 2-pyridone-containing human rhinovirus (hrv) 3c protease (3cp) inhibitors are described. these compounds are comprised of a peptidomimetic binding determinant and a michael acceptor moiety, which forms an irreversible covalent adduct with the active site cysteine residue of the 3c enzyme. the 2-pyridone-containing inhibitors typically display improved 3cp inhibition properties relative to related peptide-derived ... | 2002 | 11931615 |
| structure-based design of a parallel synthetic array directed toward the discovery of irreversible inhibitors of human rhinovirus 3c protease. | utilizing the tools of parallel synthesis and structure-based design, a new class of michael acceptor-containing, irreversible inhibitors of human rhinovirus 3c protease (hrv 3cp) was discovered. these inhibitors are shown to inhibit hrv-14 3cp with rates of inactivation ranging from 886 to 31 400 m(-1) sec(-1). these inhibitors exhibit antiviral activity when tested against hrv-14 infected h1-hela cells, with ec(50) values ranging from 1.94 to 0.15 microm. no cytotoxicity was observed at the li ... | 2002 | 11985469 |
| virucidal activity and cytotoxicity of the liposomal formulation of povidone-iodine. | two drug formulations of povidone-iodine (pvp-i)--an aqueous pvp-i solution (betaisodona) and a liposomal pvp-i formulation--were tested for their virucidal activity and cytotoxicity in cell culture. as to the virudical activity against influenza a virus, herpes simplex virus type 1, adenovirus type 8 and human rhinovirus type 14, the liposomal formulation of pvp-i proved to be approximately as active as the aqueous one. half maximum cytotoxic pvp-i concentrations were 0.01-0.07% for aqueous pvp ... | 2002 | 12062394 |
| species-specific receptor recognition by a minor-group human rhinovirus (hrv): hrv serotype 1a distinguishes between the murine and the human low-density lipoprotein receptor. | human rhinoviruses (hrv) of the minor receptor group use several members of the low-density lipoprotein receptor superfamily for cell entry. these proteins are evolutionarily highly conserved throughout species and are almost ubiquitously expressed. their common building blocks, cysteine-rich ligand binding repeats about 40 amino acids in length, exhibit considerable sequence similarity. various numbers of these repeats are present in the different receptors. we here demonstrate that hrv type 1a ... | 2002 | 12072496 |
| sequence requirements for viral rna replication and vpg uridylylation directed by the internal cis-acting replication element (cre) of human rhinovirus type 14. | until recently, the cis-acting signals required for replication of picornaviral rnas were believed to be restricted to the 5' and 3' noncoding regions of the genome. however, an rna stem-loop in the vp1-coding sequence of human rhinovirus type 14 (hrv-14) is essential for viral minus-strand rna synthesis (k. l. mcknight and s. m. lemon, rna 4:1569-1584, 1998). the nucleotide sequence of the apical loop of this internal cis-acting replication element (cre) was critical for rna synthesis, while se ... | 2002 | 12097561 |
| synthesis of new 3-methylthio-5-aryl-4-isothiazolecarbonitriles with broad antiviral spectrum. | the isothiazole derivative 3-methylthio-5-(4-obn-phenyl)-4-isothiazolecarbonitrile, coded is-50, which in previous studies had exhibited a broad antipicornavirus spectrum of action, was selected as the model for the synthesis of a new series of 3-methylthio-5-aryl-4-isothiazolecarbonitriles. these compounds were prepared in good yield (from 66 to 82%) by alkylation of 3-methylthio-5-(4-hydroxyphenyl)-4-isothiazolecarbonitrile with suitable bromides in the presence of acetone; only the 4-cyanophe ... | 2002 | 12103435 |
| synergism between rhinovirus infection and oxidant pollutant exposure enhances airway epithelial cell cytokine production. | of the several factors believed to exacerbate asthmatic symptoms, air pollution and viral infections are considered to be particularly important. although evidence indicates that each of these respiratory insults individually can increase asthma severity in susceptible individuals, we know little about the extent to which exposure to environmental oxidant pollutants can influence the course of respiratory viral infection and its associated inflammation. to investigate the interaction of these tw ... | 2002 | 12117643 |
| crystal structure of a human rhinovirus that displays part of the hiv-1 v3 loop and induces neutralizing antibodies against hiv-1. | we report the 2.7 a resolution structure of a chimeric rhinovirus, mn-iii-2, that displays part of the hiv-1 gp120 v3 loop and elicits hiv-neutralizing antibodies. the v3 loop insert is dominated by two type i beta turns. the structures of two adjacent tripeptides resemble those of analogous segments in three fab/v3 loop peptide complexes. although two of the three corresponding antibodies bind and neutralize mn-iii-2 well, only one of the three can bind without significant rearrangement. these ... | 2002 | 12121655 |
| a thermosensitive mutant of hrv2 2a proteinase: evidence for direct cleavage of eif4gi and eif4gii. | infection of mammalian cells with picornaviruses like entero-, rhino-, and aphthoviruses leads to an inhibition of cap-dependent cellular protein synthesis by the cleavage of both translation initiation factors, eif4gi and eif4gii. in entero- and rhinovirus infection this cleavage process is mediated by the viral 2a proteinase (2a(pro)). in order to discriminate between a direct mode of eif4g cleavage and an indirect cleavage via activation of a cellular proteinase, a thermosensitive 2a(pro) mut ... | 2002 | 12123803 |
| recent advances in the synthesis, design and selection of cysteine protease inhibitors. | inhibition of cysteine proteases is emerging as an important strategy for the treatment of a variety of human diseases. intense efforts involving structure-based inhibitor design have been directed toward several cysteine proteases, including cathepsin k, calpain, human rhinovirus 3c protease and several parasitic cysteine protease targets. other successful recent efforts have involved combinatorial synthesis and screening for identification of new inhibitor templates. | 2002 | 12133721 |
| the concerted conformational changes during human rhinovirus 2 uncoating. | delivery of the rhinovirus genome into the cytoplasm involves a cooperative structural modification of the viral capsid. we have studied this phenomenon for human rhinovirus serotype 2 (hrv2). the structure of the empty capsid has been determined to a resolution of better than 15 a by cryo-electron microscopy, and the atomic structure of native hrv2 was used to examine conformational changes of the capsid. the two proteins around the 5-fold axes make an iris type of movement to open a 10 a diame ... | 2002 | 12191477 |
| recognition of eukaryotic initiation factor 4g isoforms by picornaviral proteinases. | the leader proteinase (l(pro)) of foot and mouth disease virus is a papain-like cysteine proteinase. after processing itself from the polyprotein, l(pro) then cleaves the host protein eukaryotic initiation factor (eif) 4gi, thus preventing protein synthesis from capped mrna in the infected cell. we have investigated l(pro) interaction with eif4gi and its isoform, eif4gii. l(pro), expressed as a catalytically inactive fusion protein with glutathione s-transferase, binds specifically to eif4g isom ... | 2002 | 12228254 |
| evaluation of the role of respiratory viruses in acute myringitis in children less than two years of age. | the etiology of acute myringitis remains controversial although it is usually encountered in connection with acute otitis media (aom). in most cases of acute myringitis a bacterial pathogen has been detected in the middle ear fluid, but the role of respiratory viruses has remained unclear. our objective was to investigate the etiologic role of viruses in the pathogenesis of acute bullous and hemorrhagic myringitis in children <2 years of age. | 2002 | 12237595 |
| human rhinovirus 87 identified as human enterovirus 68 by vp4-based molecular diagnosis. | human rhinoviruses (hrvs) are the major cause of respiratory infections. we developed a diagnostic method for hrvs based on the reverse-transcription polymerase chain reaction (rt-pcr) and vp4-based phylogenetic analysis. a set of primers used in the rt-pcr of human enteroviruses (evs) appeared to be capable of amplifying all prototype strains of hrvs, each of which generated a 530-bp fragment. the single exception was hrv-87, which generated a 650-bp fragment, as observed in human evs. the vp4 ... | 2002 | 12403917 |
| human rhinovirus 87 and enterovirus 68 represent a unique serotype with rhinovirus and enterovirus features. | it has recently been reported that all but one of the 102 known serotypes of the genus rhinovirus segregate into two genetic clusters (c. savolainen, s. blomqvist, m. n. mulders, and t. hovi, j. gen. virol. 83:333-340, 2002). the only exception is human rhinovirus 87 (hrv87). here we demonstrate that hrv87 is genetically and antigenically highly similar to enterovirus 68 (ev68) and is related to ev70, the other member of human enterovirus group d. the partial nucleotide sequences of the 5' untra ... | 2002 | 12409401 |
| biochemical and genetic studies of the vpg uridylylation reaction catalyzed by the rna polymerase of poliovirus. | the first step in poliovirus (pv) rna synthesis is the covalent linkage of ump to the terminal protein vpg. this reaction can be studied in vitro with two different assays. the simpler assay is based on a poly(a) template and requires synthetic vpg, purified rna polymerase 3d(pol), utp, and a divalent cation. the other assay uses specific viral sequences [cre(2c)] as a template for vpg uridylylation and requires the addition of proteinase 3cd(pro). using one or both of these assays, we analyzed ... | 2003 | 12502805 |
| virus-ligand interactions: identification and characterization of ligand binding by nmr spectroscopy. | we demonstrate the detection and characterization of ligand binding to viruses via nmr. to illustrate the methodology, the interaction of an antiviral compound with human rhinovirus serotype 2 (hrv2) was investigated. specific interaction of a capsid-binding inhibitor and native hrv2 was monitored utilizing saturation transfer difference (std) nmr. std nmr experiments at atomic resolution allowed those regions of the ligand that are involved in the interaction with the virus to be determined. th ... | 2003 | 12515488 |
| human rhinovirus selectively modulates membranous and soluble forms of its intercellular adhesion molecule-1 (icam-1) receptor to promote epithelial cell infectivity. | human rhinoviruses are responsible for many upper respiratory tract infections. 90% of rhinoviruses utilize intercellular adhesion molecule-1 (icam-1) as their cellular receptor, which also plays a critical role in recruitment of immune effector cells. two forms of this receptor exist; membrane-bound (micam-1) and soluble icam-1 (sicam-1). the soluble receptor may be produced independently from the membrane-bound form or it may be the product of proteolytic cleavage of micam-1. the ratio of airw ... | 2003 | 12551926 |
| structure and function analysis of the poliovirus cis-acting replication element (cre). | the poliovirus cis-acting replication element (cre) templates the uridylylation of vpg, the protein primer for genome replication. the cre is a highly conserved structural rna element in the enteroviruses and located within the polyprotein-coding region of the genome. we have determined the native structure of the cre, defined the regions of the structure critical for activity, and investigated the influence of genomic location on function. our results demonstrate that a 14-nucleotide unpaired t ... | 2003 | 12554882 |
| unr is required in vivo for efficient initiation of translation from the internal ribosome entry sites of both rhinovirus and poliovirus. | translation of picornavirus rnas is mediated by internal ribosomal entry site (ires) elements and requires both standard eukaryotic translation initiation factors (eifs) and ires-specific cellular trans-acting factors (itafs). unr, a cytoplasmic rna-binding protein that contains five cold-shock domains and is encoded by the gene upstream of n-ras, stimulates translation directed by the human rhinovirus (hrv) ires in vitro. to examine the role of unr in translation of picornavirus rnas in vivo, w ... | 2003 | 12610110 |
| virus-induced asthma. | clinical and experimental investigations indicate that respiratory viral infections are important triggers for asthma attacks. viral upper respiratory infections have been associated with 80% of asthma exacerbations in children and 50% of all asthma episodes in adults. human rhinovirus (hrv) has been implicated as the most common virus associated with asthma episodes. the observation that the great majority of wheezing lower respiratory tract illnesses in early life are associated with acute vir ... | 2002 | 12619381 |
| increased aeroallergen-specific interleukin-4-producing t cells in asthmatic adults. | asthma, atopy and some forms of respiratory syncytial virus (rsv) disease are thought to be caused by t cells making il-4 (th2 cells). however, not all patients with similar patterns of clinical disease have the same underlying pathogenesis and the ability to detect immunopathogenic t cells by examination of the peripheral blood remains in doubt. with the prospect of specific immunotherapy for diseases caused by t cell subsets, it is important to determine whether peripheral blood mononuclear ce ... | 2002 | 12653165 |
| the processing of eif4gi by human rhinovirus type 2 2a(pro): relationship to self-cleavage and role of zinc. | the 2a proteinase (2a(pro)) of human rhinoviruses (hrvs) is a cysteine protease containing a structurally important zinc ion. in the viral polyprotein, the enzyme cleaves between the c terminus of vp1 and its own n terminus. 2a(pro) also processes the two isoforms of the cellular protein, eukaryotic initiation factor 4g (eif4g). we have shown that mature hrv2 2a(pro), when translated in vitro in rabbit reticulocyte lysates, efficiently cleaves eif4gi, although the enzyme was not immediately acti ... | 2003 | 12663811 |
| human rhinovirus 2a proteinase cleavage sites in eukaryotic initiation factors (eif) 4gi and eif4gii are different. | several picornaviruses shut down host cellular protein synthesis by proteolytic cleavage of the eukaryotic initiation factor (eif) 4gi and eif4gii isoforms. viral rna translation is maintained by a cap-independent mechanism. here, we identify the human rhinovirus 2 2a(pro) cleavage site in eif4gii in vitro as pllnv(699)*gsr; this sequence lies seven amino acids c-terminal to the cleavage site previously identified in eif4gi (lstr681*gpp). | 2003 | 12663812 |
| humanization of an anti-icam-1 antibody with over 50-fold affinity and functional improvement. | the monoclonal antibody 1a6 binds to human intercellular adhesion molecule 1 (icam-1, cd54) and inhibits infection by 90% of human rhinovirus (hrv) serotypes. to make a therapeutic molecule for preventing and treating hrv infection, we humanized a single chain antibody (scfv), 1a6, by a structure-guided complementarity-determining region (cdr) grafting procedure. our final humanized 1a6 scfv does not retain any mouse back mutations in the framework. without changing the cdr sequences, the humani ... | 2003 | 12667668 |
| poliovirus type 1 in working stocks of typed human rhinoviruses. | after eradication of circulating polioviruses, reintroduction might arise from cultured laboratory stocks, or from collections of patients' or environmental samples. in an example of a further class of risk, we recorded poliovirus type 1 in at least four working stocks of what had been identified as various serotypes of human rhinovirus. this finding emphasises the need to urgently assess the possibility of presence of poliovirus, even in apparently well-characterised stocks of other viruses, to ... | 2003 | 12686044 |
| human rhinovirus type 2 is internalized by clathrin-mediated endocytosis. | using several approaches, we investigated the importance of clathrin-mediated endocytosis in the uptake of human rhinovirus serotype 2 (hrv2). by means of confocal immunofluorescence microscopy, we show that k(+) depletion strongly reduces hrv2 internalization. viral uptake was also substantially reduced by extraction of cholesterol from the plasma membrane with methyl-beta-cyclodextrin, which can inhibit clathrin-mediated endocytosis. in accordance with these data, overexpression of dynamin k44 ... | 2003 | 12692238 |
| conformational changes, plasma membrane penetration, and infection by human rhinovirus type 2: role of receptors and low ph. | human rhinovirus type 2 (hrv2) is internalized by members of the low-density lipoprotein (ldl) receptor (ldlr) family. it then progresses into late endosomes, where it undergoes conversion from d- to c-antigenicity at ph < 5.6. upon uncoating, the viral rna is transferred into the cytoplasm across the endsosomal membrane. however, c-antigenic particles fail to attach to ldlr; this raised the question of whether the virus remains attached to the receptors and is carried to late compartments or ra ... | 2003 | 12692239 |
| asthma exacerbations in children associated with rhinovirus but not human metapneumovirus infection. | children with asthma were studied during the southern hemisphere winter and summer of 2001-2002. human rhinovirus (hrv) was significantly associated (p=.0001) with asthma exacerbations in winter and spring/summer, but not in intervening asymptomatic periods. although hrv was also found in children with upper respiratory tract infection (urti) who underwent sampling at the same time, it was present in significantly higher numbers of children with symptomatic asthma (p<.0001). human metapneumoviru ... | 2003 | 12696012 |
| detection of rhinovirus rna in middle turbinate of patients with common colds by in situ hybridization. | human rhinovirus 14 rna was determined by in situ hybridization from middle turbinate biopsies in 32 patients with diagnosed common colds and in five control individuals. twenty-two (69%) biopsies from common colds patients but none of the five control biopsies showed reactivity for human rhinovirus 14 antisense probe. the signal was detected both in the respiratory epithelium and in mucosal inflammatory cells. in situ hybridization of the middle turbinate tissue yielded more positive results th ... | 2003 | 12696124 |
| prevention of human rhinovirus infection by multivalent fab molecules directed against icam-1. | we have developed a technology for improving avidity by making bivalent, trivalent, or tetravalent recombinant polypeptides. we designed tripartite proteins consisting of the fab fragment of an antibody fused with a hinge derived from human immunoglobulin d that was further linked to polymerization domains derived from human coiled-coil proteins. we report here on the application of this method with a fab domain directed against the major human rhinovirus receptor, intercellular adhesion molecul ... | 2003 | 12709314 |
| rhinovirus infections in hematopoietic stem cell transplant recipients with pneumonia. | little is known about the impact of human rhinovirus (hrv) and coronavirus infections in hematopoietic stem cell transplant (hsct) recipients. we tested bronchoalveolar lavage (bal) samples obtained from hsct recipients with acute pulmonary infiltrates for hrv (n=122) and coronavirus (n=46) by reverse-transcriptase polymerase chain reaction. hrv rna was detected in 6 (8%) of 77 patients, and coronavirus rna was detected in 0 of 46 of bal samples from hsct recipients. the fatality rate in hrv-inf ... | 2003 | 12715308 |
| structural analysis of human rhinovirus complexed with icam-1 reveals the dynamics of receptor-mediated virus uncoating. | intercellular adhesion molecule 1 (icam-1) functions as the cellular receptor for the major group of human rhinoviruses, being not only the target of viral attachment but also the mediator of viral uncoating. the configurations of hrv3-icam-1 complexes prepared both at 4 degrees c and physiological temperature (37 degrees c) were analyzed by cryoelectron microscopy and image reconstruction. the particle diameters of two complexes (with and without rna) representing uncoating intermediates genera ... | 2003 | 12743267 |
| human rhinovirus type 16: mutant v1210a requires capsid-binding drug for assembly of pentamers to form virions during morphogenesis. | our laboratory has previously reported isolation of human rhinovirus type 16 (hrv16) mutants which depend on win 52035 to grow. a rapid rise of progeny virus infectivity occurred when drug was added late in growth cycles, suggesting that the drug-dependence lesion was at the step of virus assembly (w. wang et al., j. virol. 72:1210-1218, 1998). here, we report that capsid subunits, 5s protomers and 14s pentamers, of a drug-dependent mutant were produced normally in the absence of drug, but mutan ... | 2003 | 12743280 |
| human rhinoviruses. | human rhinoviruses are the most important causative agents of upper respiratory infections and are also implicated in more severe clinical entities. although often present, very little is known about human rhinoviruses. molecular methods have been used in the classification of this large group of viruses into two separate clades. in addition, one known serotype was found to be a member of enterovirus group d. laboratory diagnosis of human rhinovirus infection is based on reverse transcription po ... | 2003 | 12758045 |
| backbone 1h, 15n and 13c assignments for the human rhinovirus 3c protease (serotype 14). | 2003 | 12766405 | |
| human rhinovirus 2 2apro recognition of eukaryotic initiation factor 4gi. involvement of an exosite. | the 2a proteinase (2apro) of human rhinovirus 2 is a cysteine proteinase with a unique chymotrypsin-like fold. during viral replication, 2apro performs self-processing by cleaving between its own n terminus and the c terminus of the preceding protein, vp1. subsequently, 2apro cleaves the two isoforms of the cellular protein, eukaryotic initiation factor (eif) 4g. we have previously shown that hrv2 2apro can directly bind to eif4g isoforms. here we demonstrate using deletion mutants of eif4gi tha ... | 2003 | 12791690 |
| dynamic force microscopy imaging of native membranes. | we employed magnetic acmode atomic force microscopy (macmode afm) as a novel dynamic force microscopy method to image surfaces of biological membranes in their native environments. the lateral resolution achieved under optimized imaging conditions was in the nanometer range, even when the sample was only weakly attached to the support. purple membranes (pm) from halobacterium salinarum were used as a test standard for topographical imaging. the hexagonal arrangement of the bacteriorhodopsin trim ... | 2003 | 12801675 |
| a melittin-related peptide from the skin of the japanese frog, rana tagoi, with antimicrobial and cytolytic properties. | two peptides with antimicrobial and cytolytic properties were purified from an extract of the skin of tago's brown frog rana tagoi. the primary structure of one peptide (flpilgklls(10)gil.nh(2)) identifies it as a member of the temporin family, whereas the second peptide (aigsilgala(10)kglptliswi(20)knr.nh(2)) displays 78% sequence identity to melittin from the venom of the honeybee apis florea. compared with melittin, the melittin-related peptide (mrp) was equipotent in inhibiting the growth of ... | 2003 | 12804591 |
| viability of poliovirus/rhinovirus vpg chimeric viruses and identification of an amino acid residue in the vpg gene critical for viral rna replication. | picornaviral rna replication utilizes a small virus-encoded protein, termed 3b or vpg, as a primer to initiate rna synthesis. this priming step requires uridylylation of the vpg peptide by the viral polymerase protein 3d(pol), in conjunction with other viral or host cofactors. in this study, we compared the viral specificity in 3d(pol)-catalyzed uridylylation reactions between poliovirus (pv) and human rhinovirus 16 (hrv16). it was found that hrv16 3d(pol) was able to uridylylate pv vpg as effic ... | 2003 | 12805442 |
| an orally bioavailable oxime ether capsid binder with potent activity against human rhinovirus. | a series of capsid-binding compounds was screened against human rhinovirus (hrv) using a cpe based assay. the ethyl oxime ether 14 was found to have outstanding anti-hrv activity (median ic(50) 4.75 ng/ml), and unlike the equivalent ethyl ester compound 3 (pirodavir), it has good oral bioavailability, making it a promising development candidate. compound 14 illustrates that an oxime ether group can act as a metabolically stable bioisostere for an ester functionality. | 2003 | 12852746 |
| a cellular receptor of human rhinovirus type 2, the very-low-density lipoprotein receptor, binds to two neighboring proteins of the viral capsid. | the very-low-density lipoprotein receptor (vldl-r) is a receptor for the minor-group human rhinoviruses (hrvs). only two of the eight binding repeats of the vldl-r bind to hrv2, and their footprints describe an annulus on the dome at each fivefold axis. by studying the complex formed between a selection of soluble fragments of the vldl-r and hrv2, we demonstrate that it is the second and third repeats that bind. we also show that artificial concatemers of the same repeat can bind to hrv2 with th ... | 2003 | 12857919 |
| analysis of the cloverleaf element in a human rhinovirus type 14/poliovirus chimera: correlation of subdomain d structure, ternary protein complex formation and virus replication. | rna genomes of enteroviruses and rhinoviruses contain a 5'-terminal structure, the cloverleaf (cl), which serves as signal in rna synthesis. substitution of the poliovirus [pv1(m)] cl with that of human rhinovirus type 2 (hrv2) was shown previously to produce a viable chimeric pv, whereas substitution with the hrv14 cl produced a null phenotype. fittingly, the hrv14 cl failed to form a complex with pv-specific proteins 3cd(pro)-3ab or 3cd(pro)-pcbp2, considered essential for rna synthesis. it wa ... | 2003 | 12867653 |
| encephalomyocarditis virus (emcv) proteins 2a and 3bcd localize to nuclei and inhibit cellular mrna transcription but not rrna transcription. | we have followed the viral processing cascade and polyprotein precursor fates during encephalomyocarditis virus (emcv) infection of hela cells using a panel of monoclonal antibodies (mabs). within the first 2-4 h of infection, signals of antibodies specific for the 2a, 3b(vpg), 3c(pro) and 3d(pol) proteins were found to co-localize in nucleoli at the rrna synthesis and cellular protein b23 (nucleophosmin) sites. cellular fractionation identified viral protein precursor 3bcd as the common source ... | 2003 | 12921996 |
| isolation of a peptide inhibitor of human rhinovirus. | cell culture-based transdominant genetic techniques provide new methods for discovering peptide/rna modulators of cellular pathways. we applied this technology to isolate a peptide inhibitor of human rhinovirus. a green fluorescent protein (gfp)-scaffolded library of cdna fragments was expressed in hela cells from a retroviral vector and screened for inhibitors of rhinovirus-mediated cell killing. a dna clone, i421, increased cell survival in an hrv14 challenge assay from less than 0.5% to great ... | 2003 | 12951031 |