Respiratory syncytial virus infection of human respiratory epithelial cells enhances inducible nitric oxide synthase gene expression.
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The induction kinetics of the mRNA of interferon regulatory factor 1 (IRF-1), inducible nitric oxide synthase (iNOS), and proinflammatory cytokines in respiratory syncytial virus (RSV)-infected human type 2 alveolar epithelial cells (A549 cells) were analyzed semiquantitatively by RT-PCR. RSV enhanced IRF-1 and iNOS mRNA expression as early as 4 h after RSV infection and this enhancement lasted several hours. No IFN-gamma gene expression was observed during the whole course of the infection. Expression of IFN-beta, IL-1beta, and TNF-alpha genes was observed slightly at 4 h and became marked 7 h after infection. Addition of neutralizing antibodies to these cytokines to the culture had no effect on the induction of iNOS mRNA. The iNOS transcriptional activity in RSV-infected cells was significantly enhanced by an exogenous cytokine mixture (IL-1beta, TNF-alpha, and IFN-gamma). An apparent nitric oxide (NO) production was identified only when cytokines were added together with RSV infection. A significant increase of iNOS gene expression was observed in nasopharyngeal exudate cells obtained from infants during the acute phase of RSV bronchiolitis. These observations suggest that RSV infection of human respiratory epithelial cells induces the iNOS gene both in vitro and in vivo; this induction may occur rather promptly and involves transcriptional activator IRF-1 induced by the RSV infection itself. The iNOS gene, which is initially induced by RSV infection, may be further enhanced in a paracrine fashion by proinflammatory cytokines released by infection-activated inflammatory cells. (+info)
Effect of respiratory syncytial virus on subsequent allergic sensitization to ovalbumin in guinea-pigs.
(26/1345)
Children with acute respiratory syncytial virus (RSV) bronchiolitis often develop recurrent wheezing, asthma and allergic sensitization, but the role of RSV in the pathogenesis of these sequelae is unclear. This study examined whether RSV infection potentiates subsequent allergic sensitization, airway hyperresponsiveness (AHR) and airway inflammation induced by repeated exposures to aerosolized ovalbumin (OA) in guinea-pigs. Guinea-pigs received either RSV or sham inoculum, followed by exposures to OA- or saline-containing aerosols to form the following groups: 1) noninfected, nonsensitized controls (sham/saline group); 2) RSV-infected, nonsensitized animals (RSV/ saline group); 3) noninfected, OA-sensitized animals (sham/OA group); 4) RSV infection and first OA exposure on the same day (RSV/OA group), and 5) RSV infection six days prior to first OA exposure (RSV6/OA group). Three days after the final aerosol exposure, circulating OA-specific immunoglobulin (Ig)G1 antibody titres and AHR to inhalation acetylcholine challenge were measured and morphometry performed to evaluate allergic inflammation of the airways. OA-exposed animals developed OA-specific IgG1 antibodies, AHR and airway eosinophilia (sham/OA, RSV/OA and RSV6/OA groups. RSV infection alone induced significant AHR and airway eosinophilia (RSV/saline group). RSV infection, and concomitant exposure to OA (RSV/OA group) enhanced OA-specific IgG1 antibodies, but not airway eosinophilia or AHR. Such increases were not observed in the RSV6/OA group. In conclusion, respiratory syncytial virus potentiates the production of ovalbumin-specific immunoglobulin G1 antibodies in guinea-pigs, but circulating titres of these antibodies do not reflect the extent of airway hyperresponsiveness or airway inflammation. In addition, respiratory syncytial virus infection alone can produce slight increases in airway hyperresponsiveness that are associated with increased numbers of eosinophils in the airways. (+info)
Phenotypic analysis of local cellular responses in calves infected with bovine respiratory syncytial virus.
(27/1345)
Changes in lymphocyte subsets in the trachea, pulmonary tissue, bronchoalveolar lavage (BAL), peripheral blood and bronchial lymph node (BLN) of gnotobiotic calves infected with bovine respiratory syncytial virus (BRSV) were analysed by flow cytometry. Following BRSV infection, virus titres in the nasopharynx reached a peak between days 5 and 7 and infection was resolving from day 10. Although calves did not develop signs of clinical respiratory disease, there was evidence of gross pneumonia and histological changes typical of BRSV bronchiolitis, which were most extensive from day 710 of infection. Following BRSV infection there was a recruitment of CD8+ T cells into the trachea and lung, which peaked on day 10 after infection. Thus, there were approximately equal numbers of CD8+ and CD4+ T cells in the lung and trachea of uninfected calves, whereas by day 10 of infection, CD8+ cells outnumbered CD4+ cells by 3:1 in the lungs and 6:1 in the trachea of the infected calves. Although the increase in CD4+ T cells into the lungs was less marked than that of CD8+ T cells, changes in expression of CD45R, CD45RO, L-selectin and interleukin-2 receptors all suggested that CD4+ T cells were activated during BRSV infection. Changes in gamma delta T cells were not observed in BRSV-infected calves. There was a marked increase in B cells in the BLN after infection and BLN CD4+ T cells changed from the majority expressing L-selectin and CD45R in uninfected calves to a predominance of L-selectin- CD45R- CD45RO+ phenotype, 10 days after infection. In conclusion, CD8+ T cells constitute the major lymphocyte subpopulation in the respiratory tract of calves recovering from BRSV infection. (+info)
Effectiveness of RSVIG prophylaxis and therapy of respiratory syncytial virus in an immunosuppressed animal model.
(28/1345)
Respiratory syncytial virus (RSV) has emerged as a leading cause of pneumonia, with high mortality, in bone marrow transplant (BMT) recipients, as well as in other profoundly immunocompromised patients, such as myelosuppressed adults with leukemia. We tested the efficacy of immunoglobulin with high anti-RSV neutralizing antibody levels (RSVIG) for prophylaxis and therapy of RSV infection in cotton rats undergoing prolonged immunosuppression with cyclophosphamide. These animals experience persistent infection, a model which is similar to the disease seen in post-BMT humans. Both prophylaxis and therapy reduced pulmonary viral replication over 500-fold to nearly undetectable levels. In animals receiving continual immunosuppression, the use of multiple therapeutic doses of RSVIG was able to prevent rebound viral replication, though virus was not completely eliminated. (+info)
Prophylaxis with respiratory syncytial virus F-specific humanized monoclonal antibody delays and moderately suppresses the native antibody response but does not impair immunity to late rechallenge.
(29/1345)
Respiratory syncytial virus (RSV) is the most significant viral cause of lower respiratory tract disease in infants and children. This study tested the hypothesis that a humanized murine monoclonal antibody (MAb) would protect against RSV infection in mice and have minimal suppressive effect upon the immune response because it is directed against a single epitope. A humanized murine MAb (RSHZ19) was tested for both prophylaxis and treatment of RSV infection in BALB/c mice and compared with a polyclonal product. Mice were rechallenged when passively administered antibody was undetectable (day 104). RSHZ19 reduced virus titer and protected against illness when used in prophylaxis and effected rapid virus clearance when used as treatment. Polyclonal antibody was also an effective prophylaxis but required 200 times the dose in total protein. Peak neutralizing antibody responses were delayed and somewhat suppressed in the prophylactically treated groups, but mice were protected against infection on rechallenge. Secondary antibody response to rechallenge in passively immunized mice was equal to that in untreated mice. (+info)
Vaccination with pertussis toxin alters the antibody response to simultaneous respiratory syncytial virus challenge.
(30/1345)
Many bacterial toxins, including pertussis toxin (PT), exert potent adjuvant effects on antibody synthesis to coadministered antigens. In these studies, we examined whether locally or peripherally administered PT similarly altered the antibody isotype selection to replicating virus after intranasal (inl) challenge. Mice primed intramuscularly with PT and inl with respiratory syncytial virus (RSV) produced RSV-specific antibodies of the IgG2a isotype at a level similar to that of unprimed controls, with some increase in IgG1 production. Mice primed inl with both PT and RSV showed elevated RSV-specific IgG1, increased serum IgE levels, and increased interleukin (IL)-4 in lung supernatants. Splenocytes from these animals produced increased IL-4 when stimulated in vitro with RSV or PT antigens after infection. These results suggest that PT can influence the local production of IL-4 to alter the humoral and cellular immune responses to viral infection as well as to coadministered antigens. (+info)
Respiratory syncytial virus G and/or SH protein alters Th1 cytokines, natural killer cells, and neutrophils responding to pulmonary infection in BALB/c mice.
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BALB/c mice sensitized to vaccinia virus expressed G protein of respiratory syncytial virus (RSV) develop a Th2-type cytokine response and pulmonary eosinophilia when challenged with live RSV. In this study, BALB/c mice were immunized or challenged with an RSV mutant lacking the G and SH proteins or with DNA vaccines coding for RSV G or F protein. F or G protein DNA vaccines were capable of sensitizing for pulmonary eosinophilia. The absence of the G and/or SH protein in the infecting virus resulted in a consistent increase both in pulmonary natural killer cells and in gamma interferon and tumor necrosis factor expression, as well as, with primary infection, a variable increase in neutrophils and CD11b(+) cells. The development of pulmonary eosinophilia in formalin-inactivated RSV-vaccinated mice required the presence of the G and/or SH protein in the challenge virus. These data show that G and/or SH protein has a marked impact on the inflammatory and innate immune response to RSV infection. (+info)
Antigenic and genetic characterization of twenty-six strains of human respiratory syncytial virus (subgroup A) isolated during three consecutive outbreaks in Havana city, Cuba.
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Twenty-six human respiratory syncytial virus strains (subgroup A) isolated from three outbreaks in Havana City during the period 1994/95, 1995/96 and 1996/97 were analyzed to determine their antigenic and genetic relationships. Analyses were performed by monoclonal antibodies and restriction mapping (N gene) following amplification of the select region of the virus genome by polymerase chain reaction. All isolated strains were classified as subgroup A by monoclonal antibodies and they showed a restriction pattern NP4 that belonged to subgroup A. Thus the results obtained in this work, showed a close relation (100%) between antigenic and genetic characterization of the isolated strains in our laboratory. These methods permit the examination of large numbers of isolates by molecular techniques, simplifying the researchs into the molecular epidemiology of the virus. (+info)