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PubMed1982

Antigenic groupings of 90 rhinovirus serotypes.

We have completed production in rabbits of potent antisera to the 90 classified rhinovirus serotypes by using methods previously described (M. K. Cooney and G. E. Kenny, Proc. Soc. Exp. Biol. Med. 133:645-650, 1970). Systematic testing by neutralization tests has revealed significant numbers of cross-relationships among rhinovirus types, some of which have already been reported. Herein, our observations are compared with cross-reactions reported in National Institutes of Health reference guinea pig antisera. Also, original rhinovirus isolates, representing serotypes known to be antigenically related to other rhinoviruses, were tested against rabbit antisera to the related serotypes. These tests revealed extensive antigenic variation among isolates identified as rhinovirus 12:78 or 36:58, which are reciprocally related pairs, 41, reciprocally related to 13, and 67, which is related to both 9 and 32. If the rhinovirus serotypes were grouped according to antigenic relationships, 50 types could be included in 16 groups.

Animals↗
PubMed1986

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 rhinovirus serotypes assayed. In addition, the receptor antibody protects HeLa cells from infection by three coxsackievirus A serotypes. The receptor antibody was unable to protect cells from infection by a wide range of other RNA and DNA viruses. Using the receptor antibody and human rhinovirus type 15, we determined that the cellular receptor utilized by the vast number of human rhinovirus serotypes is present only on cells of human origin, with the exception of chimpanzee-derived cells. The receptor antibody has a strong affinity for the cellular receptor as evidenced by its rapid binding kinetics and ability to displace previously bound human rhinovirus virions from receptors. No viral variants were identified which could bypass the receptor blockage.

Animals↗
PubMed2006

S-nitrosothiols regulate cell-surface pH buffering by airway epithelial cells during the human immune response to rhinovirus.

Human rhinovirus infection is a common trigger for asthma exacerbations. Asthma exacerbations and rhinovirus infections are both associated with markedly decreased pH and ammonium levels in exhaled breath condensates. This observation is thought to be related, in part, to decreased activity of airway epithelial glutaminase. We studied whether direct rhinovirus infection and/or the host immune response to the infection decreased airway epithelial cell surface pH in vitro. Interferon-gamma and tumor necrosis factor-alpha, but not direct rhinovirus infection, decreased pH, an effect partly associated with decreased ammonium concentrations. This effect was 1) prevented by nitric oxide synthase inhibition; 2) independent of cyclic GMP; 3) associated with an increase in endogenous airway epithelial cell S-nitrosothiol concentration; 4) mimicked by the exogenous S-nitrosothiol, S-nitroso-N-acetyl cysteine; and 5) independent of glutaminase expression and activity. We then confirmed that decreased epithelial pH inhibits human rhinovirus replication in airway epithelial cells. These data suggest that a nitric oxide synthase-dependent host response to viral infection mediated by S-nitrosothiols, rather than direct infection itself, plays a role in decreased airway surface pH during human rhinovirus infection. This host immune response may serve to protect the lower airways from direct infection in the normal host. In patients with asthma, however, this fall in pH could be associated with the increased mucus production, augmented inflammatory cell degranulation, bronchoconstriction, and cough characteristic of an asthma exacerbation.

Cell Line↗
PubMed1997

Prevention of rhinovirus infection in chimpanzees by soluble intercellular adhesion molecule-1.

Intercellular adhesion molecule-1 (ICAM-1) is the cell surface receptor for the major class of human rhinoviruses, and tICAM453, a truncated, soluble form of ICAM-1, has been shown previously to be a potent in vitro inhibitor of rhinovirus. In this report, we have investigated the in vivo efficacy of tICAM453 for the prophylaxis of rhinovirus serotype 16 infection in the chimpanzee. Because chimpanzees do not show clinical symptoms of infection after rhinovirus challenge, infection was followed by measuring antirhinovirus serum antibody responses and detection of virus shedding. By both of these measures, intranasal application of tICAM453 was efficacious in preventing rhinovirus infection in chimpanzees subsequently challenged with infectious doses of virus. These results suggest that the use of soluble rhinovirus receptor to inhibit virus binding to host cells should be feasible in humans.

Administration, Intranasal↗
PubMed1999

Rhinovirus and respiratory syncytial virus in wheezing children requiring emergency care. IgE and eosinophil analyses.

This cross-sectional emergency department study of 70 wheezing children and 59 control subjects (2 mo to 16 yr of age) examined the prevalence of respiratory viruses and their relationship to age, atopic status, and eosinophil markers. Nasal washes were cultured for respiratory viruses, assayed for respiratory syncytial virus (RSV) antigen, and tested for coronavirus and rhinovirus RNA using reverse transcription-PCR (RT-PCR). Also evaluated were eosinophil numbers and eosinophil cationic protein (ECP) in both nasal washes and serum, along with total IgE and specific IgE antibody in serum. Respiratory viruses were detected in 82% (18 of 22) of wheezing infants younger than 2 yr of age and in 83% (40 of 48) of older wheezing children. The predominant pathogens were RSV in infants (detected in 68% of wheezing subjects) and rhinovirus in older wheezing children (71%), and both were strongly associated with wheezing (p < 0.005). RSV was largely limited to wheezing children younger than 24 mo of age, but rhinovirus was detected by RT-PCR in 41% of all infants and in 35% of nonwheezing control subjects older than 2 yr of age. After 2 yr of age the strongest odds for wheezing were observed among those who had a positive RT-PCR test for rhinovirus together with a positive serum radioallergosorbent testing (RAST), nasal eosinophilia, or elevated nasal ECP (odds ratios = 17, 21, and 25, respectively). Results from this study demonstrate that a large majority of emergent wheezing illnesses during childhood (2 to 16 yr of age) can be linked to infection with rhinovirus, and that these wheezing attacks are most likely in those who have rhinovirus together with evidence of atopy or eosinophilic airway inflammation.

Adolescent↗
PubMed2000

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 resulted in synthesis of cytokines (IL-1, IL-6, G-CSF, and GM-CSF) and CXC chemokines (IL-8, epithelial neutrophil-activating protein-78, and growth-related oncogene-alpha), evident 24-72 h postinfection. Rhinovirus infection induced a time- and dose-dependent increase in tyrosine phosphorylation of p38 kinase, which peaked 30 min postinfection and remained elevated for 1 h. Treatment of infected cells with SB 239063, a potent pyridinyl imidazole inhibitor of p38 kinase, resulted in up to 100% inhibition of mediator production and partially reduced levels of IL-8 mRNA as determined by quantitative RT-PCR. Treatment with SB 239063 had no effect on virus replication and was not cytotoxic at concentrations </= 70 microM. These studies provide the first evidence that early activation of p38 kinase by rhinovirus infection is a key event in regulation of virus-induced cytokine transcription, and may provide a new target for inhibition of symptoms and airway inflammation associated with rhinovirus infection.

Bronchi↗
PubMed2004

Induction of mucin secretion from human bronchial tissue and epithelial cells by rhinovirus and lipopolysaccharide.

AIM: To examine the effects of rhinovirus and lipopolysaccharide (LPS) on mucin secretion from bronchial tissue and epithelial cells in vitro. METHODS: Human small bronchial tissue fragments (HSBTF) and human bronchial epithelial cells (HBEC) were cultured with rhinovirus 16 and LPS, respectively and culture supernatants were collected for mucin measurement. To determine mucin levels in the culture supernatants, a MUC5AC enzyme linked immunosorbent assay and an enzyme linked lectin assay procedure with dolichos biflorus agglutinin (DBA) were developed, and mucin release was expressed as percentage increased (or decreased) secretion over baseline level. RESULTS: A concentration-dependent release of DBA mucin and MUC5AC mucin were observed when HSBTF were infected with various concentrations of rhinovirus 16 at 37 degree. The maximum-induced DBA mucin and MUC5AC mucin release were approximately 258 % and 83 % over baseline. The response of HSBTF to rhinovirus was completely abolished by metabolic inhibitors. Rhinovirus was also able to induce a concentration-dependent release of DBA mucin and MUC5AC mucin from primarily cultured HBEC. LPS 100 mg/L was able to provoke up to approximately 19 % and 54 % increase in DBA and MUC5AC mucin release over baseline, respectively from HSBTF, and 3.1 % and 57 % increase from HBEC at 20 h. Soybean trypsin inhibitor (SBTI) 30 mg/L was able to inhibit LPS-induced mucin release from HSBTF and HBEC. CONCLUSION: Rhinovirus is able to induce mucin secretion from human bronchial tissue and bronchial epithelial cells in vitro. LPS can induce MUC5AC mucin release from HSBTF and HBEC.

Bronchi↗
PubMed1990

Effect of bovine fibroblast interferon on rhinovirus infection in calves.

The prophylactic/therapeutic activity of natural bovine fibroblast interferon (BoF-IFN) against bovine rhinovirus infection in calves was assessed. Six calves were each given 8 intranasal inoculations of partially purified BoF-IFN (3.25 x 10(5) U at 8 AM, 11 AM, 5 PM, and 8PM on day 1 and 8 AM, 11 AM, 2 PM, and 5PM on day 2), and 6 calves were given placebo. All calves were challenge exposed with 10(5.1) TCID50 of bovine rhinovirus after the first 2 treatments (6 hours after the first IFN or placebo treatment). Nasal excretion of rhinovirus, IFN concentration in the nasal secretions, and nasal secretion and serum rhinovirus antibodies were measured before and at selected times after calves were inoculated. Interferon-treated calves excreted rhinovirus in their nasal secretions in lesser amounts (mean value, 0.84 log10 TCID50/ml vs 1.58 log10 TCID50/ml on postchallenge exposure days 1 and 2; (P less than 0.05) and for a shorter duration (P less than 0.05) than did placebo-treated calves. No calves developed clinical signs of respiratory tract illness. Rhinovirus antibody titer was not significantly different between IFN- and placebo-treated calves.

Administration, Intranasal↗
PubMed1989

Modulation of thymosin alpha 1 and thymosin beta 4 levels and peripheral blood mononuclear cell subsets during experimental rhinovirus colds.

Cellular immune response to localized upper respiratory viral infection was studied in two groups of healthy volunteers infected with an unnumbered rhinovirus serotype (Hanks). In the first group of 18 volunteers, serum levels of thymosin alpha 1 rose on day 5 following rhinovirus challenge. This observation was confirmed in a second group of 20 normal volunteers inoculated with the same rhinovirus strain; there was a slight increase in thymosin alpha 1 levels on day 3 and a significant rise on day 5 (p less than .001). There was also a significant rise in serum thymosin beta 4 levels on day 5 (p less than .001). Serum cortisol rose in parallel with thymosin alpha 1 on day 5 after rhinovirus inoculation, but there was no direct relationship between individual changes in cortisol and thymosin alpha 1 levels. Enumeration of peripheral blood mononuclear cell subpopulations during rhinovirus infection revealed a significant increase in total lymphocytes on day 5 (p less than .01), but not on day 3. The rise in total lymphocyte count was attributable to an increase in T lymphocytes (CD3+) (p less than .05), cytotoxic/suppressor (CD8+) cells (p less than .01) and natural killer (CD16+ cells) (p less than .05). This is the first report of thymic hormone modulation by a virus, and suggests that local rhinovirus infection of the upper respiratory tract has systemic effects and induces cellular immune responses.

Adult↗
PubMed1970

The rhinoviruses of man.

Rhinoviruses, prominent agents of the common cold syndrome in man, are small ribonucleic acid (rna) viruses resembling enteroviruses in their physicochemical properties except for high density and lability to acid pH. Rhinoviruses are propagated in human and monkey cells. Highest titers of virus are obtained in HeLa cell cultures. Rhinoviruses produce characteristic cytopathic effect in diploid fibroblasts. A plaque assay in HeLa cells is useful for their titration. The rhinovirus group includes many serotypes. Although rhinoviruses cause predominantly upper respiratory tract symptoms, they may on occasion infect the lower respiratory tract. Volunteers with specific antibody, when challenged with homotypic rhinovirus, are protected against the common cold.

Common Cold↗
PubMed2002

Rhinovirus and coronavirus infection-associated hospitalizations among older adults.

Rhinoviruses and coronaviruses are recognized as the major causes of the common cold syndrome. The role of these viruses in more serious respiratory illnesses resulting in hospitalization is less well defined. During a winter when influenza A infection was prevalent, 100 elderly adults hospitalized because of cardiopulmonary illnesses were evaluated for rhinovirus and coronavirus infection. Patients who tested negative for influenza or respiratory syncytial virus had nasal swab samples tested for rhinovirus, coronavirus OC43, and coronavirus 229E by reverse-transcription polymerase chain reaction and for coronaviruses by serologic testing. Twelve percent of patients had rhinovirus or coronavirus identified (rhinovirus, 4 patients; coronavirus 229E, 4 patients; coronavirus OC43, 3 patients; and mixed rhinovirus/coronavirus 229E infection, 1 patient). All patients had significant underlying diseases. Although all patients recovered, the mean length of stay was 8 days; 4 persons had pneumonia, and 1 required ventilator support. These data suggest that rhinoviruses and coronaviruses may be associated with serious respiratory illnesses in frail older adults.

Aged↗
PubMedDate not supplied

[Development of optimal conditions for isolation of rhinoviruses].

When 366 dispensary patients with respiratory diseases were examined in Moscow during the period December 1969--May 1971, 49 strains of rhinoviruses were isolated out of which 21 strains were identified as type 48. Using Eagle's medium with a single set of amino acids and vitamins for isolation rhinoviruses were isolated in 4.7% of cases, empdoying Eagle's medium with a double set of amino acids and vitamins in 16% of cases. Virus isolation experiments were carried out in HeLa-Bristol cell cultures and diploid strain of skin-muscle cells KM-13-70 in the presence of 30 mM MgCl2 and 2% aminopeptide. The isolation rate of rhinoviruses in both the cell cultures was approximately similar. The average duration of time for isolation of rhinoviruses in diploid cells was 13.4 days, in HeLa-Bristol cells 15 days. All rhinovirus strains were isolated within 3 passages. In addition to rhinoviruses, from the same group of patients 25 Coxsackie A-21 strains, 12 adenovirus strains and 2 herpesvirus strains were isolated using Eagle's medium with double set of amino acids and vitamins.

Adenoviridae↗
PubMed2000

Differential detection of rhinoviruses and enteroviruses RNA sequences associated with classical immunofluorescence assay detection of respiratory virus antigens in nasopharyngeal swabs from infants with bronchiolitis.

To define the role of enteroviruses and human rhinoviruses as etiological agents in childhood bronchiolitis, clinical aspirates from 84 infants admitted to hospital with symptoms of obstructive bronchiolitis were tested by picornavirus RT-PCR assay, adenovirus PCR assay and classical immunofluorescence antigen detection of common respiratory viral agents. Respiratory syncytial viruses (A&B) were detectable in 45 of 84 (53.6%) nasopharyngeal aspirates from infants with bronchiolitis, whereas coronaviruses, influenza viruses, and parainfluenza viruses were not detectable in the same samples. Adenoviruses were detectable by PCR in 11 of 84 (13.1%) nasopharyngeal swabs. By using a picornavirus RT-PCR assay followed by a differential molecular hybridisation, rhinovirus and enterovirus RNA sequences were detected in 16 of 84 (19%) and in 10 of 84 (11.9%) of the nasopharyngeal swabs tested. Positive human rhinovirus or enterovirus RT-PCR assay, however, was the only evidence of respiratory infection in 8 of 84 (9.5%) and in 7 of 84 (8.33%) of the studied patients. Respiratory syncytial viruses, human rhinoviruses, adenoviruses, and enteroviruses occur in dual infections detected in 18 of 84 (21.4%) respiratory samples tested. The median duration of stay in hospital was not significantly different between the patients demonstrating a single viral infection and those with a dual viral infection (6.22 +/- 2.07 vs. 5. 04 +/- 0.95 days; P > 0.05). In summary, combination of molecular and classical detection assays of common viruses can be used to demonstrate enterovirus and human rhinovirus respiratory infection in childhood bronchiolitis, and provides an improved approach to obtain new insights into concomitant viral respiratory tract infection in infants.

Antigens, Viral↗
PubMed1988

Contribution of rhinoviruses to respiratory viral infections in childhood: a prospective study in a mainly hospitalized infant population.

A prospective study was carried out to investigate the contribution of rhinoviruses to respiratory viral infections in children and to investigate the influence of age, passive smoking, and educational level of the head of the family on the clinical course of viral respiratory disease. Nasopharyngeal aspirates from 519 infants (90.8% inpatients, 9.2% outpatients) were screened for the presence of rhinoviruses, respiratory syncytial virus (RSV), adenoviruses, parainfluenza virus types 1, 2, 3, influenza virus types A and B, and enteroviruses by tissue culture isolation procedure, enzyme-linked immunosorbent assay, and/or indirect immunofluorescence method. The total detection rate was 42.4%. The rate decreased with increasing age. Higher detection rates were observed in specimens from children suffering from a more severe respiratory disease, and the highest rate of virus-positive specimens was found in those aged 0-6 months. Second to RSV (23.1%), rhinoviruses were the most frequently recovered pathogens found in 11.8% of children with acute respiratory tract infections (RTI). In the age group 0-6 months the majority of severe respiratory illnesses was due to RSV. In infants aged 6 months to 1 year a decrease in the number of severe illnesses caused by RSV and an increase in the number of children suffering from a more severe RTI caused by rhinoviruses was found. With the possible exception of one group of children infected with rhinoviruses, a negative effect of passive smoking on the incidence and severity of viral RTI could not be established. A beneficial effect of breast feeding on the severity of viral RTI could not be definitely demonstrated.

Austria↗
PubMed1989

Evaluation of a new enzyme-linked immunosorbent assay (ELISA) in the diagnosis of rhinovirus infection.

This study describes the evaluation of a newly developed ELISA for the direct detection of rhinovirus antigens in nasal washings. Of 54 volunteers inoculated with 100 TCID50 of human rhinovirus type 2 (HRV-2), 50 (96.6%) and 32 (59%) excreted antigen and virus on at least 1 of 3 days investigated, respectively. Thirty-three (61%) had significant rises in rhinovirus-specific IgA by ELISA. Twelve (22%) developed symptoms of colds. Generally the ELISA detected antigen more frequently in volunteers later in the course of infection and provided evidence of infection in a higher proportion of asymptomatic compared with symptomatic volunteers. On the other hand, virus isolation detected virus more frequently earlier in the course of infection and in a higher proportion of symptomatic compared with asymptomatic volunteers. We conclude that rhinovirus antigen detection by ELISA is a simple, rapid, sensitive, and practical test to diagnose a rhinovirus infection and potentially a viable alternative to virus isolation.

Antigens, Viral↗
PubMed2006

Echinacea extracts modulate the production of multiple transcription factors in uninfected cells and rhinovirus-infected cells.

Extracts of Echinacea purpurea are widely used for the prevention and treatment of common colds, coughs, bronchitis and other upper respiratory infections, many of which are caused by rhinoviruses (RVs). Recent reports have indicated that rhinoviruses can stimulate the release of various pro-inflammatory cytokines and chemokines from cultured nasal and bronchial human epithelial cells, and several transcription factors (TFs) have been implicated in this process. The effects of Echinacea treatment and rhinovirus infection on the activation of a range of transcription factors were evaluated by means of a protein/DNA array analysis. The BEAS-2B cell line was used as the model, and nuclear extracts of uninfected cells and rhinovirus-14 infected cells were examined with and without treatment with one of two chemically different Echinacea extracts. It was found that both Echinacea extracts increased the nuclear content of more than 30 transcription factors, including the 12 pro-inflammatory factors examined, such as NFkB, AP-1, AP-2 and STATs 1-6. Virus infection resulted in a more dramatic increase in these same TFs. However, when RV-infected cells were treated with either of the two Echinacea extracts, TF levels were reduced to low levels, although the pattern of the reductions was different for the two extracts. These results indicate that rhinovirus infection of epithelial cells, and treatment with Echinacea extracts, led to profound effects on numerous transcription factors, which could explain the previously observed modulation of secreted cytokines and chemokines, as well as other signaling pathways. In addition, the results could help to explain the beneficial effects of Echinacea consumption.

Cell Line↗
PubMed1989

Use of synthetic oligonucleotide probes to detect rhinovirus RNA.

Current methods of detecting a human rhinovirus (HRV) infection are either based on isolation of virus in appropriate susceptible cell lines, which is time-consuming and requires considerable expertise, or are dependent on knowing the serotype. The existence of over 100 immunologically distinct serotypes makes serotype specific assays, such as ELISA, unsuitable for general diagnostic assays. In this study a general rhinovirus assay is described which utilises synthetic oligonucleotides as probes in a filter hybridization assay. The probes are designed to bind to short but highly conserved regions of the rhinovirus genome. Indeed, the probes successfully detected all 57 rhinovirus serotypes tested. Furthermore, the test was used to demonstrate rhinovirus infection in clinical samples from 57 volunteers, inoculated with HRV, collected on six consecutive days. Clinical samples were taken prior to inoculation and on days 2-7 after inoculation. The filter hybridization assay gave results comparable to virus culture on days 2 and 3 post-inoculation, but was more sensitive on subsequent days.

Base Sequence↗
PubMed1990

Analysis of the structure of a common cold virus, human rhinovirus 14, refined at a resolution of 3.0 A.

Human rhinovirus 14 has a pseudo T = 3 icosahedral structure in which 60 copies of the three larger capsid proteins VP1, VP2 and VP3 are arranged in an icosahedral surface lattice, reminiscent of T = 3 viruses such as tomato bushy stunt virus and southern bean mosaic virus. The overall secondary and tertiary structures of VP1, VP2 and VP3 are very similar. The structure of human rhinovirus 14, which was refined at a resolution of 3.0 A [R = 0.16 for reflections with F greater than 3 sigma(F)], is here analyzed in detail. Quantitative analysis of the surface areas of contact (proportional to hydrophobic free energy of association) supports the previously assigned arrangement within the promoter, in which interactions between VP1 and VP3 predominate. Major contacts among VP1, VP2 and VP3 are between the beta-barrel moieties. VP4 is associated with the capsid interior by a distributed network of contacts with VP1, VP2 and VP3 within a promoter. As the virion assembly proceeds, the solvent-accessible surface area becomes increasingly hydrophilic in character. A mixed parallel and antiparallel seven-stranded sheet is composed of the beta C, beta H, beta E and beta F strands of VP3 in one pentamer and beta A1 and beta A2 of VP2 and the VP1 amino terminus in another pentamer. This association plays an essential role in holding pentamers together in the mature virion as this contact region includes more than half of the total short non-bonded contacts between pentamers. Contacts between protomers within pentamers are more extensive than the contacts between pentamers, accounting in part for the stability of pentamers. The previously identified immunogenic regions are correlated with high solvent accessibility, accessibility to large probes and also high thermal parameters. Surface residues in the canyon, the putative cellular receptor recognition site, have lower thermal parameters than other portions of the human rhinovirus 14 surface. Many of the water molecules in the ordered solvent model are located at subunit interfaces. A number of unusual crevices exist in the protein shell of human rhinovirus 14, including the hydrophobic pocket in VP1 which is the locus of binding for the WIN antiviral agents. These may be required for conformational flexibility during assembly and disassembly. The structures of the beta-barrels of human rhinovirus 14 VP1, VP2 and VP3 are compared with each other and with the southern bean mosaic virus coat protein.

Amino Acid Sequence↗