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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 than RT-PCR (47%) or virus culture (34%) assayed from nasopharyngeal aspirates, but no statistical significant differences were observed (P = 0.265, P = 0.425, respectively). The results indicated that in situ hybridization procedure was slightly more sensitive than PCR assays and classical culture for the detection of human rhinovirus infection of upper respiratory tract. However, in situ hybridization procedure appeared to be an interesting methodology to investigate the physiopathology of respiratory tract infection by rhinoviruses.

Adult↗

Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction.

OBJECTIVE: To determine the frequencies of human rhinovirus (HRV), respiratory syncytial virus (RSV), and coronavirus (HCV) infection in children with acute otitis media (AOM). METHODS: Middle ear fluids (MEF) collected by tympanocentesis and nasopharyngeal aspirates (NPA) at the time of the AOM diagnosis were examined by reverse transcriptase polymerase chain reaction for HRV, RSV, and HCV RNA. PATIENTS: Ninety-two children aged 3 months to 7 years during a 1-year period. RESULTS: Virus RNA was detected in a total of 69 children (75%) and in 44 MEF samples (48%) and 57 NPA samples (62%) at the time of AOM diagnosis. HRV RNA was detected in both MEF and NPA in 18 (20%), in MEF alone in 4 (4%), and in NPA alone in 10 (11%). RSV was detected in both MEF and NPA in 12 (13%), in MEF alone in 5 (5%), and in NPA alone in 9 (10%). HCV RNA was detected in both MEF and NPA in 5 (5%), in MEF alone in 2 (2%), and in NPA alone in 9 (10%). Dual viral infections were detected in 5% of children. HRV and RSV were detected simultaneously in 2 MEF samples and in 2 NPA samples; RSV and HCV were detected in 1 NPA sample. Bacterial pathogens were detected in 56 (62%) MEF from 91 children. Viral RNA was detected in 20 (57%) MEF of 35 bacteria-negative and in 25 (45%) of 56 bacteria-positive MEF samples. No important differences in the risk of treatment failure, relapse, or occurrence of late secretory otitis media were noted between children with virus-positive and virus-negative MEF aspirates. CONCLUSION: These findings highlight the importance of common respiratory viruses, particularly HRV and RSV, in predisposing to and causing AOM in young children.

Acute Disease↗

Antiviral effect of hyperthermic treatment in rhinovirus infection.

Human rhinoviruses (HRV) are recognized as the major etiologic agents for the common cold. Starting from the observation that local hyperthermic treatment is beneficial in patients with natural and experimental common colds, we have studied the effect of brief hyperthermic treatment (HT) on HRV replication in HeLa cells. We report that a 20-min HT at 45 degrees C is effective in suppressing HRV multiplication by more than 90% when applied at specific stages of the virus replication cycle. Synthesis of virus proteins is not affected by HT, indicating that the target for treatment is a posttranslational event. The antiviral effect is a transient cell-mediated event and is associated with the synthesis of the 70-kDa heat shock protein hsp70. Unlike poliovirus, rhinovirus infection does not inhibit the expression of hsp70 induced by heat. The possibility that hsp70 could play a role in the control of rhinovirus replication is suggested by the fact that a different class of HSP inducers, the cyclopentenone prostaglandins PGA1 and delta 12-PGJ2, were also effective in inhibiting HRV replication in HeLa cells. Inhibition of hsp70 expression by actinomycin D prevented the antiviral activity of prostaglandins in HRV-infected cells. These results indicate that the beneficial effect of respiratory hyperthermia may be mediated by the induction of a cytoprotective heat shock response in rhinovirus-infected cells.

Antiviral Agents↗

UHRF1 restricts HCoV-229E infection through epigenetic silencing of the viral receptor APN.

The emergence of SARS-CoV-2 has posed significant threats to global health, particularly for the older population. Similarly, common human coronaviruses, such as HCoV-229E, which typically cause mild cold-like symptoms, can lead to severe diseases, underscoring the need to understand virus-host interactions and identify host factors contributing to viral pathogenesis and disease progression. In this study, we perform a genome-wide CRISPR knockout screen using HCoV-229E and identify UHRF1 as a potent restriction factor. Mechanistically, UHRF1 suppresses HCoV-229E infection by downregulating the expression of its cell entry receptor, APN, through promoter hypermethylation. Focused CRISPR activation screens of UHRF1-downregulated genes confirm the critical role of APN in HCoV-229E infection and identify additional genes (e.g., SIGLEC1, PLAC8, and heparan sulfate biosynthesis genes) contributing to the restrictive functions of UHRF1. Transcriptomic and single-cell RNA sequencing analysis reveal that UHRF1 expression decreases with age, negatively correlating with increased APN expression. This age-related decline in UHRF1 is validated in primary alveolar macrophages from elderly individuals, which exhibit heightened susceptibility to HCoV-229E compared to those from younger individuals. Our findings highlight UHRF1 as a key age-related host defense factor against coronavirus and provide insights into the epigenetic regulation of viral entry receptors.

Animals↗

Paranasal sinus bony structures and sinus functioning during viral colds in subjects with and without a history of recurrent sinusitis.

OBJECTIVES/HYPOTHESIS: The objective was to assess the impact of ostial obstruction and anatomical variations on paranasal sinus functioning during viral colds with computed tomography (CT) in subjects with and without a history of sinusitis. STUDY DESIGN: Cross-sectional study. METHODS: Twenty-three volunteers with a history of recurrent sinusitis and 25 subjects without such history who had an early (symptoms for 2-4 d) natural cold were examined by taking viral specimens and CT scans and recording symptoms. The pathological sinus changes in the CT scans were scored, and several paranasal bony anatomical variations recorded. RESULTS: Viral origin of the cold was identified in 32 (67%) subjects, similarly in the two groups. Ostiomeatal obstruction and anatomical variations were equally frequent in the subjects with and without a sinusitis history (17 of 23 vs. 17 of 25 for ostial obstruction and 17 of 23 vs. 20 of 25 for at least one variation, respectively). However, in the case of ostiomeatal obstruction the combined CT score of ethmoidal and maxillary sinuses was significantly higher in the subjects with a sinusitis history than in those without (mean +/- SD, 3.0 +/- 0.9 vs. 2.3 +/- 1.2 [P =.05, t test]). In the sinusitis-prone subjects, several variations were associated significantly with various pathological sinus CT changes (septal deviation, horizontally situated processus uncinatus, large concha bullosa, and laterally concave concha media), whereas in the control subjects, only the presence of Haller cells was related to sphenoidal sinus disease. CONCLUSION: Ostiomeatal complex obstruction and bony anatomical variations seem to have a greater impact on the functioning of paranasal sinuses during viral colds in sinusitis-prone subjects than in subjects without a sinusitis history. These differences may be associated with the increased risk of bacterial sinusitis.

Adult↗

Molecular diagnosis of human rhinovirus infections: comparison with virus isolation.

To compare the sensitivity and specificity of RT-PCR with that of virus isolation in the detection of human rhinoviruses, we tested nasopharyngeal aspirates from 200 patients on the 1st and 7th days after the onset of the common cold. An assay utilizing a short amplicon in the conserved 5' noncoding region was found highly sensitive. Of 192 positive samples altogether, 65 were found positive by RT-PCR only, 6 were positive by isolation exclusively, and 121 gave positive results in both tests.

Common Cold↗

Infections as contributing factors to atopic dermatitis.

Certain cutaneous viral infections, such as Herpes simplex, vaccinia and varicella infections are known to occasionally run an usually severe course in AD. Patients with AD display increased frequencies of recurrent cold sores and Herpes zoster and they also have increased antibody titers to Epstein-Barr virus. Heavy colonization of the skin with staphylococci and streptococci is common. The findings of increased severity and/or frequencies of these infections in AD may be explained by dysfunctional cell-mediated immunity and by cutaneous changes associated with AD. There is suggestive, but not any firm evidence, that infections play a causal role in the precipitation and exacerbation of AD. Infections are thus, in most cases, probably consequences rather than causes of the disease.

Biomechanical Phenomena↗

Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection.

To test the hypothesis that rhinovirus (RV)-induced immune responses influence the outcome of RV infections, we inoculated 22 subjects with allergic rhinitis or asthma with RV16. Nasal secretions and induced sputum were repeatedly sampled over the next 14 d. RV16 infection increased nasal granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-8, which was accompanied by neutrophilia in blood and nasal secretions. Nasal G-CSF correlated closely with increased blood neutrophils (r(s) = 0.69, p < 0.005), whereas nasal neutrophils correlated with both G-CSF (r(s) = 0.87, p < 0.001) and IL-8 (r(s) = 0.75, p < 0.001). Although similar relationships were present in sputum, changes in sputum neutrophils and G-CSF with RV16 infection were relatively modest. In addition, virus-induced changes in the sputum interferon-gamma-to-IL-5 messenger RNA ratio were inversely related to both peak cold symptoms (r(s) = -0.60, p < 0.005) and the time to viral clearance (undetectable picornavirus RNA). These results indicate that airway IL-8 and G-CSF are closely associated with virus-induced neutrophilic inflammation during an experimental RV infection in atopic volunteers. In addition, the balance of airway T-helper cell type 1 (Th1)- and Th2-like cytokines induced by RV infection may help determine the clinical outcome of common cold infections, raising the possibility that the individual subject's immune response, rather than atopic status per se, is important in this regard.

Adolescent↗

[The analysis of cytokines in cerebrospinal fluid (CSF) in two cases of non-herpetic acute limbic encephalitis (NHALE)].

We report two cases of non-herpetic acute limbic encephalitis (NHALE) which showed elevation of interleukin (IL)-6 in the cerebrospinal fluid (CSF). [Case 1] The patient was a 25-year-old woman who was admitted to another hospital because of fever and severe headache, following common cold. After the admission, she developed severe disturbance of consciousness and suffered from generalized convulsions, and was then transferred to our hospital. The CSF examination revealed neither pleocytosis nor elevation of total protein. Her consciousness improved by intravenous administration of high-dose methylprednisolone, but mild retrograde amnesia and symptomatic epilepsy remained as sequelae. [Case 2] The patient was a 58-year-old man who was admitted to our hospital because of fever, severe headache, and mild disturbance of consciousness, following common cold. After the admission, he exhibited marked psychiatric symptoms and severe amnestic syndrome. The CSF examination revealed mild lymphocytic pleocytosis and mild elevation of total protein. His clinical symptoms improved markedly by intravenous administration of high-dose methylprednisolone, but mild retrograde amnesia and personality changes remained. Cranial MRI showed reversible high signal intensity lesions in bilateral hippocampi and amygdaloid bodies on diffusion weighted images (DWI) in both cases. No laboratory findings suggesting herpes simplex virus infection or malignancy were detected in either case. In the CSF analysis of cytokines including IL-1 beta, IL-2, IL-6, IL-10, tumor necrosis factor alpha, and interferony gamma, only IL-6 was elevated in both cases. We recognized four clinical features in both cases as follows: 1. the episode of preceding infection such as common cold, 2. appearance of reversible high signal intensity lesions in bilateral hippocampi and amygdaloid bodies on DWI, 3. elevation of only IL-6 in CSF, and 4. marked neurological improvement by intravenous administration of high-dose methylprednisolone. We speculate that the immune reaction of the host might play some significant roles in the pathogenesis of NHALE, based on these four clinical features.

Acute Disease↗

[Transient, prolonged, combined sicca syndrome of the eyes and mouth. Occurrence along with a common cold in an 8-year-old girl].

A girl of eight years fell ill with signs of common cold and bronchitis. Already on the second day of illness, before any treatment was started, she showed symptoms of a sicca-syndrome, beginning in the eyes, later the mouth. Ophthalmologic examination showed keratitis filiformis, histology of the salivary glands in the mucosa of the mouth was normal. Local substitution therapy led to subjective improvement. The disorder of secretion persisted for four months only, then rapid restitutio ad integrum of tears and saliva production occurred. Pathogenetically a parainfectious immunologic mechanism seems probable. During the observed period there were significant changes of antibody titers against RS-virus and streptococci, but it is not possible to identify the cause of the illness really. We conclude that a sicca-syndrome with normal histology of mouth-mucosa-glands is not necessarily prognostically infavorable.

Antibodies, Viral↗

[Considerations on atypical acute bronchopneumopathies].

The cases were studied of 109 patients admitted to the 2nd General Medical Division of the Umberto I Hospital in Turin in the course of a year. The study revealed 99 bacterial infections and 10 atypical forms including 7 mycoplasma pneumoniae and 3 virus infections. The importance of suspecting atypical pneumopathies is therefore emphasised and despite the technical difficulties that may at times arise, tests for the less common aetiological agents are recommended.

Acute Disease↗

Protective responses in mice to vaccination with multiply administered cold-adapted influenza vaccine reassortants and wild-type viruses.

Protective responses to influenza vaccine reassortants derived from the cold-adapted (ca) donor strains A/Leningrad/134/17/57 and B/USSR/60/69 and wild-type epidemic viruses were studied in two strains of mice. Preliminary experiments revealed that, when mixtures of three viruses were inoculated intranasally to mice with 50 microliters containing 10(6) EID50 per 200 microliters (10(5.4) EID50 per mouse), interference between strains did not occur. However, interference with the growth of the influenza reassortant B/60/32/R took place if its concentration in the mixture was reduced to 10(5) (10(4.4) per mouse) or if it was inoculated at 10(6) EID50 (10(5.4) per mouse) in the presence of the influenza reassortant R/34 and two other influenza A epidemic strains; interference was unrelated to serological responses to infection with B/60/32/R. Despite evidence of interference, mice inoculated with the same mixtures in two identical doses, three weeks apart, were able to clear a challenge from each of seven homotypic and heterotypic influenza A and B strains. Heterotypic clearance of influenza A challenge viruses was greater following mixed infection, indicating that common determinants within the surface antigen glycoproteins contributed to immune responses which were broader than could be expected to be induced by parenteral vaccination.

Administration, Intranasal↗

Smoking, alcohol consumption, and susceptibility to the common cold.

OBJECTIVES: This study was conducted to test the supposition that both smoking and consuming alcohol suppress host resistance to viral infections. METHODS: The relations between smoking, alcohol consumption, and the incidence of documented clinical colds were prospectively studied among 391 subjects intentionally exposed to one of five respiratory viruses and 26 subjects given saline. Clinical colds were defined as clinical symptoms verified by the isolation of virus or by an increase in virus-specific antibody titer. Analyses included control variables for demographics; body weight; virus; and environmental, immunological and psychological factors. RESULTS: Smokers were at greater risk for developing colds than nonsmokers because smokers were more likely both to develop infections and to develop illness following infection. Greater numbers of alcoholic drinks (up to three or four per day) were associated with decreased risk for developing colds because drinking was associated with decreased illness following infection. However, the benefits of drinking occurred only among nonsmokers. CONCLUSIONS: Susceptibility to colds was increased by smoking. Although alcohol consumption did not influence risk of clinical illness for smokers, moderate alcohol consumption was associated with decreased risk for nonsmokers.

Adult↗

Acute infections of the respiratory tract in children.

Although respiratory infections are the commonest childhood diseases, they remain some of the most poorly understood. With identification of viruses as the causes of most respiratory diseases as well as controlled epidemiological studies, the understanding to acute respiratory infections is gradually increasing. Problems still exist, however, in clinically differentiating bacterial from viral infections and in evaluation the host-organism interaction.

Acute Disease↗