The respiratory virus "explosion".
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Herpes simplex virus commonly causes 'cold sores', the virus often becoming latent after the primary infection and recrudescing at intervals. Six glycoproteins have been described in the virion and in the membranes of infected cells; much of the host's immune response is directed against these molecules. The functions of individual glycoproteins in the disease process and in the induction of different components of the immune response are beginning to be unravelled, which should help provide a strategy for the creation of an effective subunit vaccine against the virus.
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Four agents which were obtained from adults with common colds were cultivated and identified-one was influenza type B and the others were parainfluenza viruses of types 2 and 4. Their cultivation was assisted by the use of organ cultures of human embryo tracheal or nasal epithelium. They infected and caused typical common colds in volunteers.
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Human rhinoviruses (HRVs), the single most important etiologic agent of common colds, are small viruses composed of an icosahedral protein shell that encapsidates a single, positive RNA strand. Multiplication of HRVs occurs in the cytoplasm of the host cell. To produce infection, HRVs must first attach to specific cellular receptors embedded in the plasma membrane. Ninety percent of HRVs immunogenic variants use as receptor intercellular adhesion molecule-1 (ICAM-1), a cell surface glycoprotein that promotes intercellular signaling in processes derived from inflammation response. As HRV receptor, ICAM-1 positions the virus to within striking distance of the membrane, and then triggers a conformational change in the virus that ultimately results in delivery of the viral RNA genome into the cytoplasm, across a lipid bilayer. The interaction between ICAM-1 and HRVs has been analyzed by the combination of crystal structures of HRVs and ICAM-1 fragments with electron microscopy reconstructions of the complexes. The resulting molecular models are useful to address questions about receptor recognition, binding specificity, and mechanisms by which ICAM-1 induces virus uncoating.
Respiratory tract viruses are particularly significant causes of illness and death in children and in the elderly. Vaccines offer the possibility of decreasing the severity and complications of viral respiratory disease, but development has been delayed by numerous factors. First, there are more than 200 serologically distinct RNA and DNA virus species and strains which cause an essentially similar spectrum of disease. Some re-infect at high efficiency despite little antigenic variation, while others exhibit extensive coat protein variability. Vaccine candidates show variable efficacy in partially immune adults, the immunocompromised and the elderly, and may be ineffective or pathogenic in neonates or in the presence of maternal antibodies. However, effective childhood vaccines are essential to prevent severe disease due to respiratory syncytial virus (RSV) and parainfluenza and to reduce virus transmission to adults. A number of promising vaccines are in clinical trial, and it is likely that vaccines against RSV and parainfluenza will be licensed within the next 5-10 years. Mucosal delivery and the use of novel adjuvants offers the prospect of better vaccines against influenza. The ultimate goal is to develop multivalent mucosal vaccines offering protection against a spectrum of respiratory infections.
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We investigated in a pilot study on healthy young subjects whether a common cold or a vaccination with influenza virus antigens within 10 days influenced the number and subsets of inflammatory cells in the bronchoalveolar lavage (BAL) fluid. The total number of BAL-cells was about doubled in the common cold group, yet no consistent changes in overall cell distribution was found. Among BAL-lymphocytes the ratio of helper-inducer over suppressor-cytotoxic lymphocytes (THI/TCS) tended to be increased in both groups, due to a lower percentage of TCS-cells, which was significant in the vaccination group only. In the blood, on the contrary, the THI/TCS ratio was significantly decreased in both groups due to a drop in THI-cells; in addition, the proportions of E-Rosette (+) T-cells and of activated (Ia+) T-cells were slightly increased. In conclusion, only minor changes in inflammatory BAL-cells were observed, which, however, may interfere with the effects of other diseases.
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