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PubMed1994

Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases.

The picornavirus family includes several pathogens such as poliovirus, rhinovirus (the major cause of the common cold), hepatitis A virus and the foot-and-mouth disease virus. Picornaviral proteins are expressed by direct translation of the genomic RNA into a single, large polyprotein precursor. Proteolysis of the viral polyprotein into the mature proteins is assured by the viral 3C enzymes, which are cysteine proteinases. Here we report the X-ray crystal structure at 2.3 A resolution of the 3C proteinase from hepatitis A virus (HAV-3C). The overall architecture of HAV-3C reveals a fold resembling that of the chymotrypsin family of serine proteinases, which is consistent with earlier predictions. Catalytic residues include Cys 172 as nucleophile and His 44 as general base. The 3C cleavage specificity for glutamine residues is defined primarily by His 191. The overall structure suggests that an intermolecular (trans) cleavage releases 3C and that there is an active proteinase in the polyprotein.

3C Viral Proteases↗
PubMed1997

Changes in nasal nitric oxide concentration associated with symptoms of common cold and treatment with a topical nasal decongestant.

Nitric oxide (NO) is known to play a role in the non-specific host defence mechanism. Furthermore, it has been proposed that NO may be important in respiratory defence against the viruses which cause the common cold. Indeed, elevated NO levels have previously been observed in orally expired air during upper respiratory tract infection (URTI). We wanted to investigate further the role of NO in the host response to URTI. Total nasal airway resistance (tNAR) and nasal NO levels were obtained during symptomatic URTI in 97 subjects. Of these, 80 received treatment with either oxymetazoline or a placebo spray. Post-treatment tNAR and NO levels were obtained 60 min after treatment. Measurements of NO were also repeated 4-6 weeks later, when subjects were healthy, (n = 82). NO levels were measured using a chemiluminescence gas analyse whilst tNAR was measured using posterior rhinomanometry. The mean pre-treatment NO level (1063 +/- 541 ppb) was shown to be reduced significantly after treatment with oxymetazoline (827 +/- 373ppb), p < 0.0001. The mean pre-treatment tNAR, 0.42 Pa cm-3 sec-1, was also reduced significantly to 0.21 Pa cm-1 sec-1 (p < 0.001) after treatment with oxymetazoline. There was no significant correlation between the change in NO levels and change in tNAR following treatment with oxymetazoline (p. corrected for ties = 0.011, p = 0.98. No significant difference was found between NO levels obtained during URTI (1130 +/- 444 ppb) when compared to values obtained when healthy (1197 +/- 361 ppb), p = 0.25. These results demonstrate that treatment with a topical nasal decongestant spray causes a reduction in nasal NO levels. We propose that this occurs as an indirect consequence of the vasoconstrictor actions of oxymetazoline. Since no change in NO levels was observed during URTI, we propose that the NO synthase responsible for NO production in the nose responds in a different manner to that in the lungs.

Administration, Topical↗
PubMed2003

Sociability and susceptibility to the common cold.

There is considerable evidence that social relationships can influence health, but only limited evidence on the health effects of the personality characteristics that are thought to mold people's social lives. We asked whether sociability predicts resistance to infectious disease and whether this relationship is attributable to the quality and quantity of social interactions and relationships. Three hundred thirty-four volunteers completed questionnaires assessing their sociability, social networks, and social supports, and six evening interviews assessing daily interactions. They were subsequently exposed to a virus that causes a common cold and monitored to see who developed verifiable illness. Increased sociability was associated in a linear fashion with a decreased probability of developing a cold. Although sociability was associated with more and higher-quality social interactions, it predicted disease susceptibility independently of these variables. The association between sociability and disease was also independent of baseline immunity (virus-specific antibody), demographics, emotional styles, stress hormones, and health practices.

Adolescent↗
PubMed1999

The American coneflower: a prophylactic role involving nonspecific immunity.

OBJECTIVE: In humans, considerable circumstantial evidence exists that indicates soluble root extracts of the American coneflower, genus Echinacea, may act to ameliorate virus-mediated afflictions, such as the common cold, influenza, and even AIDS and virus-based tumors. This study was designed to quantify, in normal mice, Echinacea-mediated, quantitative, dynamic changes, with time on both mature and precursor cells, of all the hemopoietic and immune-cell lineages in the spleen and bone marrow. DESIGN: A specific, commercially prepared potent extract of Echinacea root was provided daily in the diet for either 1 week or 2 weeks with the aim of establishing a possible mechanism of action for this herb. RESULTS: The data revealed that natural-killer (NK) cells and monocytes, both mediators of nonspecific immunity and well-demonstrated killers of virus-containing cells, were numerically and significantly increased in both the bone marrow and the spleen as early as 1 week after beginning treatment with the dietary herb. In contrast to our observations with NK cells and monocytes, the sizes of all other hemopoietic and immune cell populations in these two organs remained at control levels even after 2 weeks of daily dietary Echinacea. CONCLUSIONS: The work has demonstrated the specific nature of Echinacea-derived phytochemicals in acting as stimulants of those cells responsible for nonspecific immunity, as the first line of defense against virus-infected/transformed cells. The observations that these cells were elevated in the bone marrow indicates that at least one mechanism of action of this herb, is to stimulate new cell production in situ. The significant elevation of these two fundamental immune-cell populations, in normal animals, suggests a prophylactic role for this herb.

Animals↗
PubMed1990

A soluble form of intercellular adhesion molecule-1 inhibits rhinovirus infection.

Rhinoviruses belong to the picornavirus family and cause about 50% of common colds. Most rhinoviruses and some coxsackie viruses share a common receptor on human cells. The glycoprotein intercellular adhesion molecule-1 (ICAM-1) has recently been identified as the cellular receptor for the subgroup of rhinoviruses known as the major groups. ICAM-1 is a member of the immunoglobulin supergene family and is a ligand for lymphocyte function-associated antigen-1 (LFA-1); these ICAM-1/LFA-1 interactions are critical to many cell adhesion processes involved in the immunological response. Because anti-ICAM-1 antibodies can block binding of major-group rhinoviruses to cells, we considered that antagonism of virus-receptor interaction might be a way of preventing rhinovirus infection. We have constructed and purified a soluble form of the ICAM-1 molecule, which is normally membrane-bound, and demonstrated that it is a potent and specific inhibitor of rhinovirus infection.

Amino Acid Sequence↗
PubMed1970

[Corona virus].

Explore the source record for details and available documents.

Animals↗
PubMed2004

The crystal structure of the RNA-dependent RNA polymerase from human rhinovirus: a dual function target for common cold antiviral therapy.

Human rhinoviruses (HRV), the predominant members of the Picornaviridae family of positive-strand RNA viruses, are the major causative agents of the common cold. Given the lack of effective treatments for rhinoviral infections, virally encoded proteins have become attractive therapeutic targets. The HRV genome encodes an RNA-dependent RNA polymerase (RdRp) denoted 3Dpol, which is responsible for replicating the viral genome and for synthesizing a protein primer used in the replication. Here the crystal structures for three viral serotypes (1B, 14, and 16) of HRV 3Dpol have been determined. The three structures are very similar to one another, and to the closely related poliovirus (PV) 3Dpol enzyme. Because the reported PV crystal structure shows significant disorder, HRV 3Dpol provides the first complete view of a picornaviral RdRp. The folding topology of HRV 3Dpol also resembles that of RdRps from hepatitis C virus (HCV) and rabbit hemorrhagic disease virus (RHDV) despite very low sequence homology.

Amino Acid Sequence↗
PubMed2003

The common cold.

Despite great advances in medicine, the common cold continues to be a great burden on society in terms of human suffering and economic losses. Of the several viruses that cause the disease, the role of rhinoviruses is most prominent. About a quarter of all colds are still without proven cause, and the recent discovery of human metapneumovirus suggests that other viruses could remain undiscovered. Research into the inflammatory mechanisms of the common cold has elucidated the complexity of the virus-host relation. Increasing evidence is also available for the central role of viruses in predisposing to complications. New antivirals for the treatment of colds are being developed, but optimum use of these agents would require rapid detection of the specific virus causing the infection. Although vaccines against many respiratory viruses could also become available, the ultimate prevention of the common cold seems to remain a distant aim.

Adult↗
PubMed1993

Signs and symptoms in common colds.

The patterns of disease caused by five common viruses which infect the respiratory tract are described. The viruses were strains of rhinovirus types 2, 9, and 14, a strain of coronavirus type 229E and of respiratory syncytial virus. Volunteers were given nasal drops containing a low infectious dose of one of the viruses, quarantined from 2 days before to 5 days after inoculation, and examined daily by a clinician using a standard checklist of respiratory signs and symptoms. Only subjects who developed clinical illness accompanied by viral shedding and/or specific antibody production were analysed [n = 116]. The results confirm indication from earlier studies that the main difference between colds induced by different viruses is in duration of the incubation period. Patterns of symptom development were not substantially different with different viruses. Analyses of signs and symptoms in different categories, e.g. nasal symptoms v. coughing, justify treatment with different drugs either successively or simultaneously.

Adolescent↗
PubMed2003

Respiratory viruses detected in hospitalised paediatric patients with respiratory infections.

Over 200 strains of respiratory viruses cause a variety of human infections ranging from common cold to life-threatening pneumonia. Respiratory viruses implicated in this study are respiratory syncytial viruses (RSV), adenovirus, influenza viruses and parainfluenza viruses. The objective of this study is to determine the epidemiology of respiratory viruses in paediatric patients with lower respiratory tract infection. The methods used were direct antigen detection method, shell vial culture method and conventional tube culture method. The samples included in this study are paediatric patients seen in Universiti Kebangsaan Malaysia Hospital, Kuala Lumpur with suspected acute viral respiratory infection, presenting with acute laryngotracheobronchitis (croup), bronchiolitis and pneumonia. Nasopharyngeal aspirates were collected and processed almost immediately. A total of 222 specimens were received during February 1999 to January 2000 showing a dual peak pattern in the months of April and December. The mean age of the patients was 13 months. Pneumonia (77.9%) was the most common clinical diagnosis in children with lower respiratory tract infection. This was followed by bronchiolitis (19.4%) and croup (27%). Viral aetiologies were confirmed in 23.4% of the patients. The most common respiratory virus isolated or detected was RSV, followed by parainfluenza viruses, influenza viruses and adenovirus.

Bronchiolitis, Viral↗
PubMed2004

Rhinovirus detection: comparison of real-time and conventional PCR.

Rhinoviruses are important human respiratory viruses and the major causative agents of the common cold. Historically, detection of rhinovirus has been by virus culture and this was significantly improved by the use of PCR assays. Recently real-time PCR was developed but to date there have been no reported comparisons of conventional and real-time PCR assays for detection of rhinovirus. In this study, we first compared real-time PCR (SYBR Green I) to conventional PCR for the detection of rhinovirus in serially diluted standard DNA and rhinovirus stock to determine the limits of detection. Next, assays were compared for sensitivity to detect rhinovirus in cell culture with a known number of infected cells. Finally, the assays were compared using clinical samples known to contain rhinovirus. Real-time PCR was 10-fold more sensitive than conventional PCR to detect rhinovirus in standard DNA and in virus stock and >10-fold more sensitive to detect rhinovirus in cultured cells. Real-time PCR was significantly superior for detection of rhinovirus in patients' nasal aspirates (sensitivity 72% versus 39%, P < 0.05). In summary, we found that real-time PCR was more sensitive than conventional PCR and reduced post-PCR processing. Hence, real-time PCR is suitable for both research and clinical purposes.

Common Cold↗
PubMedDate not supplied

Childhood socioeconomic status and host resistance to infectious illness in adulthood.

OBJECTIVE: Low childhood socioeconomic status (SES) is a risk factor for adult morbidity and mortality primarily attributable to cardiovascular disease. Here, we examine whether childhood SES is associated with adult host resistance to infectious illness, and whether the effect is limited to a critical period of low SES exposure, can be undone by changes in childhood SES, and is explained by adult SES. METHODS: Three hundred thirty-four healthy volunteers reported their own and their parents' level of education and the ages during their childhood when their parents owned their homes. Volunteers' current home ownership was recorded from real estate records. Subsequently, they were given nasal drops containing 1 of 2 rhinoviruses and were monitored in quarantine for infection and signs/symptoms of a common cold. RESULTS: For both viruses, susceptibility to colds decreased with the number of childhood years during which their parents owned their home (odds ratios by tertiles adjusted for demographics, body mass, season, and prechallenge viral-specific immunity were 3.7 for fewest years, 2.6 and 1). This decreased risk was attributable to both lower risk of infection and lower risk of illness in infected subjects. Moreover, those whose parents did not own their home during their early life but did during adolescence were at the same increased risk as those whose parents never owned their home. These associations were independent of parent education level, adult education and home ownership, and personality characteristics. CONCLUSIONS: A marker of low income and wealth during early childhood is associated with decreased resistance to upper respiratory infections in adulthood. Higher risk is not ameliorated by higher SES during adolescence and is independent of adult SES.

Adolescent↗
PubMed1993

Respiratory viruses and exacerbations of asthma in adults.

OBJECTIVE: To study the role of respiratory viruses in exacerbations of asthma in adults. DESIGN: Longitudinal study of 138 adults with asthma. SETTING: Leicestershire Health Authority. SUBJECTS: 48 men and 90 women 19-46 years of age with a mean duration of wheeze of 19.6 years. 75% received regular treatment with bronchodilators; 89% gave a history of eczema, hay fever, allergic rhinitis, nasal polyps, or allergies; 38% had been admitted to hospital with asthma. MAIN OUTCOME MEASURES: Symptomatic colds and asthma exacerbations; objective exacerbations of asthma with > or = 50 l/min reduction in mean peak expiratory flow rate when morning and night time readings on days 1-7 after onset of symptoms were compared with rates during an asymptomatic control period; laboratory confirmed respiratory tract infections. RESULTS: Colds were reported in 80% (223/280) of episodes with symptoms of wheeze, chest tightness, or breathlessness, and 89% (223/250) of colds were associated with asthma symptoms. 24% of 115 laboratory confirmed non-bacterial infections were associated with reductions in mean peak expiratory flow rate > or = 50 l/min through days 1-7 and 48% had mean decreases > or = 25 l/min. 44% of episodes with mean decreases in flow rate > or = 50 l/min were associated with laboratory confirmed infections. Infections with rhinoviruses, coronaviruses OC43 and 229E, influenza B, respiratory syncytial virus, parainfluenza virus, and chlamydia were all associated with objective evidence of an exacerbation of asthma. CONCLUSIONS: These findings show that asthma symptoms and reductions in peak flow are often associated with colds and respiratory viruses; respiratory virus infections commonly cause or are associated with exacerbations of asthma in adults.

Adult↗