Search PubMedSearch

SEARCH · Search PubMed

Results for “Rhinovirus”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

Comparison of rhinovirus-sensitive HeLa cells and human embryo fibroblasts for isolation of rhinoviruses from patients with respiratory disease.

Rhinovirus-sensitive HeLa cells (HeLa "R") and human embryo lung fibroblasts (HEL) were compared for the isolation of rhinoviruses from patients with respiratory disease. In the period May 1970 to December 1974, 526 rhinoviruses were isolated from 517 patients, 32% in both cell types, 59% in HeLa "R" only, and 9% in HEL only. The annual isolations in HeLa "R" were between 1.7 and 4 times greater than in HEL cells and may have been due to changes in the sensitivity of the cells or the prevalence of serotypes favoring the HeLa "R" cells. Acid lability was more easily demonstrated in HeLa "R" than in HEL cells, because the infectivity titers obtained were 10- to 100-fold higher.

Cell Line

Demonstration of dual rhinovirus infection in humans by isolation of different serotypes in human heteroploid (HeLa) and human diploid fibroblast cell cultures.

The ability to isolate rhinoviruses in human heteroploid cell cultures was investigated by inoculating HeLa cells (HeLa M) with specimens previously shown to be positive in human diploid cell cultures. The 135 positive specimens selected were representative of 22 different rhinovirus types, and 4 to 9 specimens were available for each serotype. Specimens were inoculated into human diploid fetal tonsil fibroblasts (FT), HeLa cells with 30 mM Mg2+, and HeLa cells without increased Mg2+. One hundred twelve rhinovirus strains (83%) were reisolated in FT cells, whereas 76 rhinovirus strains (56%) were recovered in HeLa cells with 30 mM Mg2+. All strains recovered in FT were the same serotype as that originally recovered in diploid cells, but five of the HeLa cell isolates (3.7% of total specimens) were different serotypes, indicating dual rhinovirus infections. Four rhinovirus serotypes, (3, 42, 48, and 70) were recovered in HeLa but not in diploid cells; these serotypes were rare in our previous studies. Isolation of rhinovirus in FT cells was usually accomplished at first passage, whereas rhinovirus cytopathic effects in HeLa cells were not observed at first passage, but required one, two, or (rarely) three blind passages. Only 28 rhinoviruses (21%) were recovered in HeLa cells without increased Mg2+; however, three serotypes, types 16, 36, and 58, were recovered as effectively in HeLa cells, with or without added Mg2+, as they were in FT cells. In general, rhinoviruses were less efficiently recovered in HeLa cells; however, certain serotypes may be detected better by HeLa cells.

Cell Line

Sensitivity of rhinoviruses to human leukocyte and fibroblast interferons.

Rhinoviruses were tested for sensitivity to human interferon from two sources: human leukosytes induced with Sendai virus and human diploid fibroblasts induced with polyriboinosinic-polyribocytidylic acid. Twenty-five serotypes of rhinovirus were tested against fibroblast interferon in HeLa cells, and five serotypes were evaluated in fibroblast cultures against fibroblast and leukocyte interferons. Sensitivity varied widely in the HeLa cell assay; rhinovirus type 10 was inhibited by approximately 20-40 units of interferon, whereas rhinovirus type 15 was not inhibited by 5,120 units; the significance of this observation is unclear. In contrast, when fibroblast cultures were used in the assay system, five selected serotypes, including rhinovirus types 10 and 15, had similar levels of sensitivity (0.5-5.0 units) to fibroblast or leukocyte interferon.

Cell Line

The spread of rhinoviruses in the Soviet Union (USSR) and in Czechoslovakia (CSSR) and the role of their pathology.

Virological, serological and immunofluorescence studies revealed circulation of rhinoviruses of the strains 1A, 1B, 2, 3, 7, 9, 10, 12, 13, 14, 16-23, 27, 29-33, 42, 48, 53, 56, 60 and 69 on the territory of Czechoslovakia and the Soviet Union. According to virological results, type 48 predominated and was followed in frequency of occurrence by types 27, 14 and 16 in the USSR and 30, 1A and 31 in the CSSR. RV infection in adults with ARD diseases was the aetiology in 28.5% of cases. Among the causative agents of acute rhinitis, rhinosinusitis and otitis, rhinovirus infection makes up a large proportion. Interrelation has been found between rhinovirus infection and chronic inflammation of the mucosa of the nose, the accessory sinuses and the ears. Prolonged course of rhinovirus infection and isolation of the virus in the late stages of disease (1-4 months after its onset) support the presumption that rhinoviruses promote chronicity of inflammation. RV was isolated from patients with chronic pneumonia from the lower respiratory passages (bronchial secretion). Rhinoviraemia was found in a child who died of ARD.

Adolescent

Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic susceptibility to childhood-onset asthma.

Asthma is a complex disease caused by genetic and environmental factors. Epidemiological studies have shown that in children, wheezing during rhinovirus infection (a cause of the common cold) is associated with asthma development during childhood. This has led scientists to hypothesize there could be a causal relationship between rhinovirus infection and asthma or that RV-induced wheezing identifies individuals at increased risk for asthma development. However, not all children who wheeze when they have a cold develop asthma. Genome-wide association studies (GWAS) have identified hundreds of genetic variants contributing to asthma susceptibility, with the vast majority of likely causal variants being non-coding. Integrative analyses with transcriptomic and epigenomic datasets have indicated that T cells drive asthma risk, which has been supported by mouse studies. However, the datasets ascertained in these integrative analyses lack airway epithelial cells. Furthermore, large-scale transcriptomic T cell studies have not identified the regulatory effects of most non-coding risk variants in asthma GWAS, indicating there could be additional cell types harboring these "missing regulatory effects". Given that airway epithelial cells are the first line of defense against rhinovirus, we hypothesized they could be mediators of genetic susceptibility to asthma. Here we integrate GWAS data with transcriptomic datasets of airway epithelial cells subject to stimuli that could induce activation states relevant to asthma. We demonstrate that epithelial cultures infected with rhinovirus significantly upregulate childhood-onset asthma-associated genes. We show that this upregulation occurs specifically in non-ciliated epithelial cells. This enrichment for genes in asthma risk loci, or 'asthma heritability enrichment' is also significant for epithelial genes upregulated with influenza infection, but not with SARS-CoV-2 infection or cytokine activation. Additionally, cells from patients with asthma showed a stronger heritability enrichment compared to cells from healthy individuals. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.

Preprint

Rhinoviruses: kinetics of ultraviolet inactivation and effects of UV and heat on immunogenicity.

The kinetics of ultraviolet inactivation for two human rhinoviruses and poliovirus were compared. No major differences in the rates of ultraviolet inactivation were detectable. All viral preparations inactivated by ultraviolet irradiation induced neutralizing antibody in guinea pigs. In contrast, when guinea pigs were immunized with a heat inactivated rhinovirus preparation, little or no neutralizing antibody was elicited. Immune electron microscopy of the heated rhinovirus preparations revealed the presence of particles resembling empty capsids. These results suggest that rhinoviruses and enteroviruses are affected in a similar manner when subjected to ultraviolet or heat inactivation.

Antibodies, Viral

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 zinc levels are those that contain capsid protein sequences. Furthermore, added zinc is bound to human rhinovirus type 1A capsids and prevents them from forming crystals. Zinc-resistant mutants display antigenic alterations in coat proteins. These results suggest that zinc complexes with rhinovirus coat proteins and alters them so that they cannot function as substrates for proteases or as reactants in the assembly of the virus particles.

Capsid

Physicochemical characterization of two serologically unrelated equine rhinoviruses.

The physicochemical properties of two serologically distinct equine rhinoviruses have been examined. Each virus sedimented at approximately 160S but co-centrifugation of the two viruses in a sucrose gradient revealed a small difference in their sedimentation coefficients. The two viruses also have different buoyant densities in cesium chloride. The equine rhinovirus type 1 equilibrated as a sharp peak at 1.45 g/ml whereas the type 2 virus equilibrated as a heterogeneous band with a peak at 1.44 g/ml but ranging in density from 1.41 to 1.45 g/ml. The relative sedimentation coefficients of the two virus RNAs were 35S for rhinovirus 1 and 37S for rhinovirus 2. A limited number of base composition analyses also showed differences between the two virus RNAs. The polypeptide profile of each serotype in polyacrylamide gels was generally similar to those of other picornaviruses but the two serotypes could be distinguished readily from each other.

Antigens, Viral

Effects of rhinovirus infection of pulmonary function of healthy human volunteers.

The effects of experimentally induced rhinovirus and mycoplasmal respiratory tract infections on the pulmonary function of healthy, young, adult volunteers were investigated prospectively. Before inoculation, 12 volunteers were completely normal, whereas 9 had increased frequency dependence of compliance as their only abnormality of pulmonary function. Rhinovirus infection was induced in 8 of the completely normal volunteers, and 5 developed increased frequency dependence of compliance at the time of illness. These changes returned toward normal during the following 2 weeks and were not associated with concomitant changes in any other parameter of pulmonary function, including "closing volume". Three subjects with increased frequency dependence of compliance as their only abnormality before rhinovirus infection developed no significant change in dynamic compliance or any other abnormality in pulmonary function after infection. No changes in pulmonary function were detected in 3 volunteers with experimentally induced mycoplasmal infection. These finding suggest that although rhinovirus infections are associated primarily with upper respiratory illness, they can produce transient peripheral airway abnormalities in previously normal young adults; however, closing volumes, as well as routine pulmonary function studies, may not detect these changes.

Adult

Hand-to-hand transmission of rhinovirus colds.

Rhinovirus was transmitted from experimentally infected volunteers (donors) to susceptible recipients and the efficiencies of spread by hand-to-hand contact and large- and small-particle aerosols compared. Transmission of infection was very efficient by the hand route: 11 of 15 hand-contact exposures initiated infection, compared with one of 12 large-particle (P less than 0.005) and none of 10 small-particle (P less than 0.005) exposures. Rhinovirus was present in nine of 18 (50%) nasal swab specimens, 28 of 43 (65%) hand rinses, and seven of 18 (39%) saliva specimens of donors; geometric mean titers of positive specimens were 10(1.5), 10(1.4), and 10(1.2) tissue culture infectious dose 50/ml (TCID 50/ml), respectively. Rhinovirus was present in 20 of 43 (46%) recipient hand rinses, with a geometric mean titer of 10(1.4)TCID50/ml. Virus on donors' hands was transferred to recipients' fingers during 20 of 28 (71%) 10-second hand-contact exposures. These findings support the concept that hand contact/self-inoculation may be an important natural route of rhinovirus transmission.

Adolescent

Antigenic relationships of common rhinovirus types from disabling upper respiratory illnesses.

The frequency of the common cold has been though to be due to the existence of more than 89 different serologic types of rhinoviruses. However, in the civilian and military population studied in this area from 1962 through 1970, types 1A, 1B, 2, 23, 29, 30 and 31 accounted for 81 percent of 487 rhinoviruses isolated from individuals with respiratory illnesses. Antigenic relationships between these types and others have been demonstrated by neutralization in WI-38 cell cultures and by immunodiffusion. Types 1A and 1b, 2 and 49, 23 and 30, 29 and 44 and others are related. With specific animal antisera, heterotypic antibody titers are minimal. However, following natural infection in man with one of these related types, antibody responses to the other was almost equal to the homotype and could predictably provide cross-protection. Even with inactive T13 rhinovirus vaccine in man, protective levels of neutralizing antibody to T41 were produced. It is clear that the rates of rhinovirus colds would be greatly increased if more than 89 immunologic distinct types actually existed. An effective vaccine could be easily prepared by selection of a few appropriate types, such as 1A, 2, 23, 29 and 31.

Adolescent

Therapeutic efficacy of inosiplex (Isoprinosine) in rhinovirus infection.

Inosiplex (Isoprinosine), the paracetamidobenzoic acid salt of inosine dimethylaminoisopropanol, has shown antiviral activity in cell culture and in animals. Controlled challenge studies using the drug in a prophylactic fashion, however, have been disappointing. In vitro studies, as well as uncontrolled clinical trials, have suggested that the drug might be more effective when used therapeutically. We therefore undertook to test inosiplex in a controlled, double-blind, therapeutic study of volunteers challenged with rhinovirus. Thirty-nine volunteers were randomly divided into groups receiving either inosiplex or placebo tablets. Drug or placebo was started either at the time of, or 48 hours after challenge with rhinovirus Type 21. Illness was assessed in terms of the classical common cold symptoms, and infection was also determined by viral isolation from daily nasal wash specimens and by serum antibody rises. Five of 19 volunteers in the inosiplex group became ill, whereas 14 of 20 in the placebo group were sick (p less than 0.01). There was no difference between the control and inosiplex groups in the number of volunteers from whom rhinovirus was isolated. There was, however, a reduction in the duration of virus shedding in the inosiplex group. Seroconversion was also slightly less common in the inosiplex group. Immunologic studies suggest that inosiplex stimulates the lymphocyte mitogenic response. The results suggest that inosiplex exerts significant therapeutic benefits in rhinovirus infection.

Adult

Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic risk to childhood-onset asthma.

Asthma is a complex disease caused by genetic and environmental factors. Studies show that wheezing during rhinovirus infection correlates with childhood asthma development. Over 150 non-coding risk variants for asthma have been identified, many affecting gene regulation in T cells, but the effects of most risk variants remain unknown. We hypothesized that airway epithelial cells could also mediate genetic susceptibility to asthma given they are the first line of defense against respiratory viruses and allergens. We integrated genetic data with transcriptomics of airway epithelial cells subject to different stimuli. We demonstrate that rhinovirus infection significantly upregulates childhood-onset asthma-associated genes, particularly in non-ciliated cells. This enrichment is also observed with influenza infection but not with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or cytokine activation. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.

Humans

Clinical evaluation of prophylactic intranasal 1-phenyl-3-(4-phenyl-2-thiazolyl) guanidine (CL 88,277) medication against rhinovirus 44 challenge.

The prophylactic intranasal medication with a new antiviral compound, 1-phenyl-3-(4 phenyl-2-thiazolyl) guanidine (CL 88,277) was evaluated in humans against rhinovirus 44 challenge. One ml containing 250 mg of CL 88,277 was administered to 10 seronegative volunteers three times a day plus one dose prior to the rhinovirus challenge (32 TCID 50) and for six consecutive post-challenge days. Ten other subjects received 56% polyethylene glycol (PEG-400), the solvent of CL 88,277 at the same time. Five subjects in each of the CL 88,277-treated and placebo-treated groups developed illness. There were no differences between the two groups in the occurrence of the severe illness and of the moderate and severe illnesses. Each sign and symptom occurred almost equally in the two groups and there was no difference in their scores between the two groups. The challenge virus was isolated from both groups but the total number of the virus isolates was less and the time span of virus excretion was shorter for the drug-treated group. The post-challenge serum antibody titers were markedly lower in the drug-treated group. Prophylactic intranasal CL 88,277 medication did not affect the course of illness induced by rhinovirus 44 challenge. It appears, however, that the virus replication in the nose was reduced and as a result the serum antibody response was diminished. PEG-400 caused a transient irritation of the nasal mucosa in all recipients.

Administration, Intranasal

Human responses to two decavalent rhinovirus vaccines.

Two formalin-inactivated, decavalent rhinovirus vaccines were tested in humans for acceptability and antigenicity. Infectivity titers of the vaccine antigens were low and ranged from 10(1.5) to 10(5.5) 50% tissue culture infective doses/ml. There were minimal or no side effects to either vaccine. The first inoculation of one vaccine produced antigenic responses to 30% of the administered antigens. Limited testing for heterologous antibody responses to nonvaccine antigens showed scattered responses. These findings suggest that potent multivalent rhinovirus vaccines containing antigens selected for cross-reactivity should be tested in an attempt to develop practical control measures for rhinoviruses.

Adult

Transmission of experimental rhinovirus colds in volunteer married couples.

Communicability of rhinovirus type 16 or type 55 was studied in 24 childless couples; on partner (the donor) was infected with laboratory-grown virus. Initially, both partners lacked antibody to the challenge agent. Rates of transmission between partners were 41% and 33% for type 16 and type 55, respectively. These rates are similar to those determined in epidemiologic studies of natural rhinovirus infection. Although the mucosa of the anterior nares was shown to be highly susceptible to infection (less than one 50% tissue culture infective dose [TCID50]), transmission rarely occurred unless (1) at least 1,000 TCID50 of virus was recovered from the donor's nasal washing, (2) the donor had virus on his hands and anterior nares, (3) he was at least moderately symptomatic, and (4) he spent many hours with his spouse. Since person-to-person transfer of rhinovirus was so dependent upon time spent together and shedding of large amounts of virus by the donor, it seems possible that the chain of infection could be interrupted by environmental manipulation.

Clinical Trials as Topic

Four compounds active against rhinovirus: comparison in vitro and in volunteers.

Four unrelated compounds active against rhinovirus were compared in tissue culture, and three of them were used in volunteers challenged with rhinovirus. The compounds were the triazino-indole SKF 40491, the substituted oxadiazole GLR9-338, the imidazo-thiazole RP L9326, and the guanidine derivative ICI 73,602. The abilities of these compounds to reduce the yield of rhinovirus types 3, 4, 9, and 31 from HeLa cells or fibroblasts were compared, and a sensitive serotype was chosen for each challenge experiment in humans. In doubleblind studies volunteers received intranasal medication before and after the challenge. Daily scoring of symptoms and titration of virus in nasal washings showed that subjects treated with SKF, GL, and RP all shed less virus than their corresponding placebo groups, significantly so in the cases of GL and RP. Clinical reactions were also less severe in volunteers treated with RP.

Adolescent

Evaluation of virucidal compounds for inactivation of rhinovirus on hands.

Antimicrobial liquids and foams were applied to the hands to determine their virucidal activity against rhinoviruses. Dilute solutions (1%) of iodine in ethyl alcohol or in water were most effective in causing inactivation of rhinovirus when applied immediately after viral contamination. Iodine also had a residual virucidal activity which persisted on the hands for up to 1 h. Less effective inactivation of rhinovirus was observed with foams containing 0.23% hexachlorophene and 58% ethyl alcohol and another containing 0.2% benzalkonium chloride and 50% ethyl alcohol. Ethyl alcohol alone or in a mixture with benzyl alcohol was the least effective preparation tested.

Anti-Infective Agents, Local