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PubMed2001

Cutting edge: myeloid complement C3 enhances the humoral response to peripheral viral infection.

HSV-1 is the causative agent of cutaneous lesions, commonly referred to as cold sores. Primary exposure to the virus ordinarily occurs through the periphery, in particular through abraded skin or mucosal membranes. Under certain circumstances (e.g., in neonatals or AIDS patients), the infection becomes disseminated, often with severe consequences. Spread of HSV-1 is limited by virus-specific Ab. The development of an efficient humoral response to the virus is dependent on innate immunity component complement C3. The liver is the major source of C3, but there are also extrahepatic origins of C3 such as lymphoid macrophages. In the present study, the significance of C3 synthesis by bone marrow-derived cells was assessed by the transfer of wild-type bone marrow into irradiated C3-deficient mice. Using these chimeric mice, extrahepatic C3 was determined sufficient to initiate specific Ab and memory responses to a peripheral HSV-1 infection.

Animals↗
PubMed1987

Influenza B in households: virus shedding without symptoms or antibody response.

In the fall of 1983, 53 households were enrolled in a double-blind trial of alpha 2-interferon as an intranasal spray to prevent common colds. During the winter/spring of 1984, 26 households were infected with influenza type B, as shown by isolation of the virus (19 households) and/or significant antibody titer rises (seven households). Interferon did not prevent influenza B infection or modify resulting illness. Of 37 persons shedding virus, 12 were asymptomatic. All were older than age 12 years, and 10 did not respond with antibody by any of the five test methods employed (complement fixation, hemagglutination inhibition, enzyme-linked immunosorbent assay (ELISA), neutralization, and Western blot). In contrast, of 13 symptomatic persons shedding virus from whom sera were available, 11 had significant antibody titer rises. Infection rates were highest among teenagers, but also surprisingly high among the 11 persons observed who were aged 50 years or older, four of whom were infected. The case-to-case interval in household transmission varied between one and nine days. Longer intervals of one, two, and four months between infections among family members were also observed, suggesting repeated introductions. Neither virus isolation alone nor serologic tests was sufficient to estimate infection rates.

Adolescent↗
PubMed2006

Rhinovirus chemotherapy.

Human rhinoviruses (HRV), members of the Picornaviridae family, are comprised of over 100 different virus serotypes. HRV represent the single most important etiological agents of the common cold [Arruda, E., Pitkaranta, A., Witek Jr., T.J., Doyle, C.A., Hayden, F.G., 1997. Frequency and natural history of rhinovirus infections in adults during autumn. J. Clin. Microbiol. 35, 2864-2868; Couch, R.B., 1990. Rhinoviruses. In: Fields, B.N., Knipe, D.M. (Eds.), Virology. Raven Press, New York, pp. 607-629; Turner, R.B., 2001. The treatment of rhinovirus infections: progress and potential. Antivir. Res. 49 (1), 1-14]. Although HRV-induced upper respiratory illness is often mild and self-limiting, the socioeconomic impact caused by missed school or work is enormous and the degree of inappropriate antibiotic use is significant. It has been estimated that upper respiratory disease accounts for at least 25 million absences from work and 23 million absences of school annually in the United States [Anzueto, A., Niederman, M.S., 2003. Diagnosis and treatment of rhinovirus respiratory infections. Chest 123 (5), 1664-1672; Rotbart, H.A., 2002. Treatment of picornavirus infections. Antivir. Res. 53, 83-98]. Increasing evidences also describe the link between HRV infection and more serious medical complications. HRV-induced colds are the important predisposing factors to acute otitis media, sinusitis, and are the major factors in the induction of exacerbations of asthma in adults and children. HRV infections are also associated with lower respiratory tract syndromes in individuals with cystic fibrosis, bronchitis, and other underlying respiratory disorders [Anzueto, A., Niederman, M.S., 2003. Diagnosis and treatment of rhinovirus respiratory infections. Chest 123 (5), 1664-1672; Gern, J.E., Busse, W.W., 1999. Association of rhinovirus infections with asthma. Clin. Microbiol. Rev. 12 (1), 9-18; Pitkaranta, A., Arruda, E., Malmberg, H., Hayden, F.G., 1997. Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR. J. Clin. Microbiol. 35, 1791-1793; Pitkaranta, A., Virolainen, A., Jero, J., Arruda, E., Hayden, F.G., 1998. Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction. Pediatrics 102, 291-295; Rotbart, H.A., 2002. Treatment of picornavirus infections. Antivir. Res. 53, 83-98]. To date, no effective antiviral therapies have been approved for either the prevention or treatment of diseases caused by HRV infection. Thus, there still exists a significant unmet medical need to find agents that can shorten the duration of HRV-induced illness, lessen the severity of symptoms, minimize secondary bacterial infections and exacerbations of underlying disease and reduce virus transmission. Although effective over-the-counter products have been described that alleviate symptoms associated with the common cold [Anzueto, A., Niederman, M.S., 2003. Diagnosis and treatment of rhinovirus respiratory infections. Chest 123 (5), 1664-1672; Gwaltney, J.M., 2002a. Viral respiratory infection therapy: historical perspectives and current trials. Am. J. Med. 22 (112 Suppl. 6A), 33S-41S; Turner, R.B., 2001. The treatment of rhinovirus infections: progress and potential. Antivir. Res. 49 (1), 1-14; Sperber, S.J., Hayden, F.G., 1988. Chemotherapy of rhinovirus colds. Antimicrob. Agents Chemother. 32, 409-419], this review will primarily focus on the discovery and development of those agents that directly or indirectly impact virus replication specifically highlighting new advances and/or specific challenges with their development.

Antiviral Agents↗
PubMed2004

Deadly viral syndrome mimics.

Upper respiratory tract infections (ie, "the common cold") have several hundred causes, the most common of which include rhino-virus, coronavirus, and respiratory syncytial virus. The clinical presentation varies with symptoms. Every emergency department, no matter what the demographics, cares for patients with this constellation of symptoms. Emergency physicians examine, diagnose, and treat these disorders frequently. With increasing burdens being placed on emergency physicians, it is possible to assume a diagnosis of upper respiratory tract infection without generating a complete differential diagnosis. The challenge is to identify and recognize the distinctions between an innocuous upper respiratory tract infection and a life-threatening disease "mimic" or entities. This article discusses some of these life-threatening mimics.

Common Cold↗
PubMed1987

[Causative relations between infections and allergies in obstructive respiratory tract diseases in childhood].

Obstructive bronchitis of young babies and infants is most often caused by respiratory-syncytial (RS)- and parainfluenza viruses, to a certain extent by adenoviruses. In the school age-group rhinoviruses and to a smaller extent mycoplasma pneumoniae gain further importance. All the viruses may cause or deteriorate asthmatic attacks, as well as during common cold or on the basis of documented allergies. Proposed mechanisms of viral-infection-induced obstructive airway disease are distinct lesions of bronchial-epithelium, followed by enhanced allergen-resorption and sensitization of submucosal mast cells, establishing an allergy. Following epithelial discontinuation airway irritant receptors which are raised in sensitivity by viral toxins are exposed and stimulated. Via vago-vagal reflexes this leads to bronchoconstriction. Furthermore, in the development of bronchial hyperresponsiveness there may be participation of virus-induced blockage of adrenoceptors, basophilic and mast-cell release of mediators as well as induction of specific IgE antibodies against RS- and/or Para-influenza-viruses. Viral airway infections are supposed to influence the immunological response of T-lymphocytes and probably macrophages selectively, e.g. to regulate IgE-antibody production. Especially in children with an atopic family history the RS-viruses cause obstructive airway disease. During acute respiratory-virus infections using electron microscopy marked pathological changes of bronchial-epithelium can be demonstrated causing disturbance or even stopage of mucus-transport. These changes are fully reversible within weeks after airway infection. Although there is no doubt about a causative relation between respiratory-tract infection and allergy, hardly any prediction for development of asthma bronchiale in later life, after having suffered from virus-induced obstructive airway disease early in life, can be made.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗
PubMed1984

Some further studies on the prediction of experimental colds in volunteers by psychological factors.

An analysis of the incidence of colds in volunteers, exposed experimentally to various rhinovirus and influenza virus challenges, confirmed an earlier report that assessments of virus shedding show a higher degree of infection by rhinovirus in Introverts than they do in Extroverts. The influenza trials however did not show such an effect. In addition, people with higher scores on a widely used self-report inventory of mild psychoneurotic symptoms tended to show more evidence of increased nasal secretion after infection by either type of virus. The specific scale showing the latter effect most clearly was that of Obsessional Symptoms. Taking account of these psychological factors greatly increased the sensitivity of a study of the beneficial effects of interferon.

Antibodies, Viral↗
PubMed1977

Trials of interferon in respiratory infections of man.

Human leucocyte interferon has been shown to prevent rhinovirus infection if given intranasally to human volunteers. This finding encourages further investigation, but it is too soon to say whether interferon is likely to be clinically useful in serious virus infections of the respiratory tract.

Administration, Intranasal↗
PubMed1997

Role of nasal interleukin-8 in neutrophil recruitment and activation in children with virus-induced asthma.

Neutrophil infiltration is a major feature in the pathogenesis of the common cold, and respiratory viral infection is the major cause of asthma exacerbations. The factors regulating the neutrophil influx are unknown. Interleukin-8 (IL-8) is a potent neutrophil chemoattractant, which has been implicated in several inflammatory diseases. In this study, we investigated the presence of IL-8 chemokine in the nasal aspirates of asthmatic children (n = 12) in whom asthma was precipitated by proven viral infection. There were increased IL-8 levels in nasal aspirates from children during the virus-induced asthma exacerbations compared with samples from the same children when they had been asymptomatic for 2 wk (medians 863 and < 20 pg/ml, respectively, p < 0.01). Biological relevance was shown in that IL-8 levels correlate with increased nasal aspirate neutrophil myeloperoxidase levels and there was also a correlation between myeloperoxidase levels and upper respiratory symptom severity. Furthermore, we purified IL-8 from these samples, and demonstrated biological neutrophil chemotactic activity. These are the first in vivo data to suggest an important role for IL-8 in neutrophil influx in proven upper respiratory viral infection associated with asthma exacerbations. We suggest that IL-8 might provide a target for therapeutic intervention in virus-induced respiratory diseases.

Asthma↗
PubMed1999

Antiviral effect of gingyo-san, a traditional Chinese herbal medicine, on influenza A2 virus infection in mice.

Gingyo-san is a crude drug containing extracts from 7 medicinal plants and fermented soybeans in a specific ratio. It has been used clinically in China as a therapeutic agent for the common cold. In the present study, we examined the antiviral effect of this agent on influenza virus infection in mice. Gingyo-san and its components were administered orally to mice 1 day before, then 1 and 4 days after the inhalation of a mouse-adopted strain of influenza A2 (H2N2) virus. After infection with a 10 LD50 of the virus, 100% of mice treated with 10 mg/kg of the agent survived as compared with a 0% survival of control mice treated with saline. Also, the mean survival days were increased and consolidation scores were decreased in treated mice as compared with those of control mice. Two components contained in the agent, extracts from Glycyrrhizae radix and Arctii fructus, expressed antiviral activities in mice infected with influenza virus. However, in vitro growth of influenza virus in MDCK cells or viability of the virus was not affected by these extracts or Gingyo-san. From these results Gingyo-san was shown to be an antiviral agent in mice infected with a lethal amount of a mouse-adopted strain of influenza A2 virus.

Animals↗
PubMed1979

Serum interferon assay as a possible test for virus infections of man.

Acute phase serum gave positive results in an interferon assay when collected from 17 out of 45 (38 per cent) patients with proven virus infection, and from none of 43 patients with other disease and none of 61 healthy subjects. Sera from 11 of 43 (26 per cent) patients with suspected virus infection were also positive. Interferon was detected in the sera of volunteers infected with respiratory viruses in strict isolation. It is suggested that the test might be used to supplement conventional tests for virus infections, and with modification may provide a useful diagnostic aid.

Adult↗