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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In adults, clinical symptoms caused by respiratory syncytial virus (RSV) are usually confined to the upper respiratory tract, whereas RSV infection in infants frequently causes bronchiolitis and pneumonia. The preferential localization of RSV infection to the upper airways may partially be due to protective immunity, but may also depend on a difference in susceptibility of epithelial cells from upper and lower airways, or on antiviral activities of bronchoalveolar macrophages (AM). In this study, we have compared the susceptibility of primary adult human nasal epithelium, primary adult human bronchial epithelium, a human bronchial epithelial cell line (BEAS-2B), and adult human AM to infection with RSV. The cell cultures were infected with multiplicities of infection (moi) of 1 and 0.1. Virus release into the supernatants was assayed at days 1, 2, 4, and 7, and the percentage of virus-positive cells determined by immunofluorescence at the same time points. Similar proportions of nasal epithelial cells (NE) and bronchial epithelial cells (BE) were infected with RSV. Approximately 50 to 75% (with moi 1) and 2 to 10% (with moi 0.1) of the cells were infected by 24 h; almost all the cells were RSV positive by day 4. However, BE released less infectious RSV than do NE. With moi 0.1, 10-fold less virus was released over 4 days of culture. By days 4 to 7, cytopathic effects (CPE) were maximal in all epithelial cell cultures, but CPE developed latest in BE infected with moi 0.1. AM were also productively infected with RSV, with peak virus production at day 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Apr
PMID:Respiratory syncytial virus infection of human primary nasal and bronchial epithelial cell cultures and bronchoalveolar macrophages. 155 Jun 81

The avian neural retina (NR) is derived from proliferating neuroectodermal precursors which differentiate after terminal mitosis and become organized in cell strata. Proliferation of postmitotic NR cells can be induced by infection with Rous sarcoma virus (RSV) and requires the expression of a functional v-Src protein. QR1 is a retina-specific gene expressed exclusively at the stage of growth arrest and differentiation during retinal development. In NR cells infected with tsPA101, an RSV mutant conditionally defective in pp60v-src mitogenic capacity, QR1 expression is downregulated in proliferating cells at 37 degrees C and is fully restored when the cells become quiescent as a result of pp60v-src inactivation at 41 degrees C. We were able to arrest proliferation of tsPA101-infected quail NR cells expressing an active v-Src protein by serum starvation at 37 degrees C. This allowed us to investigate the role of cell growth in regulating QR1 transcription. We report that QR1 transcription is stimulated in growth-arrested cells at 37 degrees C compared with that in proliferating cells maintained at the same temperature. Growth arrest-dependent stimulation of QR1 transcription requires the integrity of the A box, a previously characterized cis-acting element responsible for QR1 transcriptional stimulation upon v-Src inactivation and during retinal differentiation. We also show that formation of the C1 complex on the A box is increased upon growth arrest by serum starvation in the presence of an active v-Src oncoprotein. Thus, the C1 complex represents an important link between cell cycle and developmental control of QR1 gene transcription during NR differentiation and RSV infection. By using antibodies directed against different Maf proteins of the leucine zipper family and competition with Maf consensus site-containing oligonucleotides in a gel shift assay, we show that the C1 complex is likely to contain a Maf-related protein. We also show that a purified bacterially expressed v-Maf protein is able to bind the A box and that the level of a 43-kDa Maf-related protein is increased upon growth arrest in infected retinal cells. Moreover, ectopic expression of c-mafI, c-mafII, and mafB cDNAs in quiescent tsPA101-infected quail NR cells is able to stimulate transcription of a QR1 reporter gene through the A box. Therefore, QR1 appears to be the first target gene for a Maf-related protein(s) in the NR.
Mol Cell Biol 1995 Oct
PMID:Transcriptional stimulation of the retina-specific QR1 gene upon growth arrest involves a Maf-related protein. 756 8

Respiratory syncytial virus (RSV) is an important respiratory pathogen that preferentially infects epithelial cells in the airway, and causes a local inflammatory response. Although it has been previously demonstrated that RSV-infected airway epithelial produce cytokines, including interleukin-8 (IL-8), which contributes to the inflammatory response, the regulation of this effect of RSV is unknown. To further characterize the mechanisms by which RSV infection triggers release of IL-8, we first exposed cultured A549 cells to RSV, and measured IL-8 release via enzyme-linked immunosorbent assays (ELISA), and IL-8 messenger RNA (mRNA) induction via Northern blot analysis. We observed a dose- and time-dependent release of IL-8 in response to RSV. The optimal dose of RSV was 10(4) TCID50/ml, and maximal release of IL-8 was measured at 72 to 96 h after infection. RSV induced a biphasic (early and late) increase in IL-8 mRNA. The early phase was independent of viral infection, whereas the more pronounced late phase required the presence of live virus and infection of the epithelium. Partial (< 50%) cytopathic effects were noted at 48 h and progressed to 75% at 96 h. The monolayer was still intact at 96 h. Inhibitors of nitric oxide, including NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME), and aminoguanidine had no effect on IL-8 release or IL-8 mRNA induction. We did, however, demonstrate a dose-dependent decrease in IL-8 release and IL-8 mRNA induction in RSV-infected epithelial treated with the antioxidants dimethyl sulfoxide (DMSO) or 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Peak effects were noted at a concentration of 2% DMSO and 50 microM DMPO. The antioxidants did not inhibit viral replication or infection. This data suggest that RSV-induced IL-8 production in airway epithelium is mediated via changes in oxidant tone. The data also suggest a potential therapeutic role for antioxidants in RSV infections.
Am J Respir Cell Mol Biol 1995 Aug
PMID:Oxidant tone regulates IL-8 production in epithelium infected with respiratory syncytial virus. 762 91

Respiratory syncytial virus (RSV) is one of the most important respiratory tract pathogens in infants and young children. The airway epithelial cells are the primary target cells for RSV infection. The airway epithelial layer is not only a physical barrier, but also plays a role in a synthesis of a variety of major inflammatory cytokines (IL-6, IL-8, GM-CSF etc.) as previously reported. Endothelin-1 (ET-1) is a potent bronchoconstrictor and vasoconstrictor factor, and involved in pathogenesis of various diseases of the respiratory tract. We hypothesized that RSV may induce the release of ET-1 from the bronchial epithelial cell line. No previous data is available regarding association between RSV infection and ET-1 release. We evaluated the effect of RSV with different concentrations of RSV (MOI 0.1, 1 and 3 pfu/cell) on bronchial epithelial cell line (A549) and measured the production of ET-1 at both protein and mRNA level. A549 cells were treated with different conditions by using LPS, heat-inactivated RSV, RSV or medium alone as control. We observed time-dependent ET-1 release by RSV-infected A549 cells at 4 h, 24 h and maximum at 72 h. ET-1 was expressed in unstimulated A549 cells and was further increased by RSV. RSV with concentration MOI 0.1 (pfu/cell) and LPS appeared to have strongest stimulation on production of ET-1. In addition, ET-1 mRNA was increased significantly by 16 h and decreased to relatively low-level at 24 h. These experiments suggested that airway epithelial cells might play a role in the local airway smooth muscle tone through the production of endothelin-1 during RSV infection.
Int J Mol Med 2000 Jul
PMID:Modulation of endothelin-1 expression in pulmonary epithelial cell line (A549) after exposure to RSV. 1085 Dec 75

Surfactant protein (SP)-A is a known opsonin for a variety of pulmonary pathogens. SP-A enhances ingestion of these pathogens by interaction with an SP-A receptor (SP-AR) found on phagocytic cells such as peripheral blood monocytes (PBMC) and alveolar macrophages. Respiratory syncytial virus (RSV) is the most important respiratory pathogen in children. Recent studies have indicated that SP-A levels may be decreased in RSV bronchiolitis and pneumonia. In this study we examined the role of SP-A in uptake of RSV by both PBMC and U937 macrophages, a human macrophage cell line known to express SP-ARs. In addition, we studied the effect of SP-A- mediated uptake of RSV on production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 by these cells because incomplete immunity to recurrent RSV infection has been partially attributed to abnormal cytokine responses by macrophages. SP-A enhanced binding and uptake of fluorescently labeled RSV (RSV-FITC) by PBMC in a dose-dependent manner, with a maximal effect seen with 10 to 15 microg/ml SP-A as measured by both percent fluorescent monocytes and linear mean fluorescence (lmf) of individual cells. SP-A also enhanced uptake of RSV-FITC by U937 macrophages, with a maximal effect seen with 20 microg/ml SP-A as measured by both percent fluorescent monocytes and lmf. With respect to TNF-alpha levels, RSV alone slightly enhanced TNF-alpha production by PBMC and decreased TNF-alpha production by U937 macrophages measured at 12 h after addition of RSV. SP-A-mediated uptake of RSV significantly enhanced TNF-alpha production by PBMC and reversed the RSV-induced depression of TNF-alpha by U937 macrophages. RSV significantly enhanced IL-10 production by both cell types, which was reversed by SP-A-mediated uptake. These findings suggest that SP-A is an important opsonin for RSV and that SP-A-mediated uptake of RSV may alter some of the unusual cytokine responses that are postulated to be involved in incomplete immunity to recurrent infection.
Am J Respir Cell Mol Biol 2000 Nov
PMID:Surfactant protein-A enhances uptake of respiratory syncytial virus by monocytes and U937 macrophages. 1106 36

Major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTLs) clear respiratory tract infections caused by the pneumovirus respiratory syncytial virus (RSV) and also mediate vaccine-induced pulmonary injury. Herein we examined the mechanism for RSV-induced MHC class I presentation. Like infectious viruses, conditioned medium from RSV-infected cells (RSV-CM) induces naive cells to coordinately express a gene cluster encoding the transporter associated with antigen presentation 1 (TAP1) and low molecular mass protein (LMP) 2 and LMP7. Neutralization of RSV-CM with antibodies to interferon (IFN)-beta largely blocked TAP1/LMP2/LMP7 expression, whereas anti-interleukin-1 antibodies were without effect, and recombinant IFN-beta increased TAP1/LMP2/LMP7 expression to levels produced by RSV-CM. LMP2, LMP7, and TAP1 expression were required for MHC class I upregulation because the irreversible proteasome inhibitor lactacystin or transfection with a competitive TAP1 inhibitor blocked inducible class I expression. We conclude that RSV infection coordinately increases MHC class I expression and proteasome activity through the paracrine action of IFN-beta to induce expression of the TAP1/LMP2/LMP7 locus, an event that may be important in the initiation of CTL-mediated lung injury.
Am J Physiol Lung Cell Mol Physiol 2001 Feb
PMID:IFN-beta mediates coordinate expression of antigen-processing genes in RSV-infected pulmonary epithelial cells. 1115 3

Respiratory syncytial virus (RSV) is one of the principal agents of bronchiolitis and pneumonia in young children. Thus, there is a strong need to make a safe and effective vaccine against the RSV infection. DNA immunization is very effective at inducing both cellular and humoral immune responses. In this study, we inserted the RSV-F gene into expression vectors, pcDNA3.1 and pQE. These constructs were transformed into C2C12 and E. coli M15 cells, respectively. The expression of the RSV-F protein was confirmed by SDS-PAGE, followed by Western blot analyses. The immunization of pcDNA3.1-RSV-F elicited both anti-RSV-F titer in mouse sera and CTL activities with mouse splenocytes. Especially, the co-administration of IL-4, or the GM-CSF gene with the RSV-F gene construct, enhanced the production of anti-RSV-F Ab. However, this enhancement disappeared by the simultaneous injection of the Th1 and Th2 type cytokine genes. The CTL activities were affected by the co-delivery of the IFN-gamma gene, but not by Th2-type cytokines.
Mol Cells 2001 Aug 31
PMID:Immune induction and modulation in mice following immunization with DNA encoding F protein of respiratory syncytial virus. 1156 30

Airway epithelial cells represent the primary cell target of respiratory syncytial virus (RSV) infection. They actively participate in the lung immune/inflammatory response that follows RSV infection by expressing chemokines, small chemotactic cytokines that recruit and activate leukocytes. Regulated on activation, normal T cell expressed, and presumably secreted (RANTES) is a member of the CC chemokine subfamily and is strongly chemotactic for T lymphocytes, monocytes, basophils, and eosinophils, cell types that are present or activated in the inflammatory infiltrate that follows RSV infection of the lung. RSV infection of airway epithelial cells induces RANTES expression by increasing gene transcription and stabilizing RNA transcripts. The signaling pathway regulating RANTES gene expression after RSV infection has not been determined. In this study, we examined the role of extracellular signal-regulated kinase (ERK) and p38, members of the mitogen-activated protein (MAP) kinase (MAPK) family, in RSV-induced RANTES production. RSV infection of alveolar epithelial cells induced increased phosphorylation and catalytic activity of ERK and the upstream kinases Raf-1 and MAP ERK kinase. Induction of the MAP signaling cascade required a replication-competent virus. RSV infection of alveolar epithelial cells also induced activation of p38 MAPK. Inhibition of ERK and p38 activation significantly reduced RSV-induced RANTES mRNA and protein secretion without affecting RANTES gene transcription or transcription factor activation. These results indicate that the MAPK signaling cascade regulates RANTES production in alveolar epithelial cells through a posttranscriptional mechanism.
Am J Physiol Lung Cell Mol Physiol 2002 Aug
PMID:MAPK activation is involved in posttranscriptional regulation of RSV-induced RANTES gene expression. 1211 98

Nerve growth factor (NGF) controls sensorineural development and responsiveness and modulates immunoinflammatory reactions. Respiratory syncytial virus (RSV) potentiates the proinflammatory effects of sensory nerves in rat airways by upregulating the substance P receptor, neurokinin 1 (NK(1)). We investigated whether the expression of NGF and its trkA and p75 receptors in the lungs is age dependent, whether it is upregulated during RSV infection, and whether it affects neurogenic inflammation. Pathogen-free rats were killed at 2 (weanling) to 12 (adult) wk of age; in addition, subgroups of rats were inoculated with RSV or virus-free medium. In pathogen-free rats, expression of NGF and its receptors in the lungs declined with age, but RSV doubled expression of NGF, trkA, and p75 in weanling and adult rats. Exogenous NGF upregulated NK(1) receptor expression in the lungs. Anti-NGF antibody inhibited NK(1) receptor upregulation and neurogenic inflammation in RSV-infected lungs. These data indicate that expression of NGF and its receptors in the lungs declines physiologically with age but is upregulated by RSV and is a major determinant of neurogenic inflammation.
Am J Physiol Lung Cell Mol Physiol 2002 Aug
PMID:Nerve growth factor and nerve growth factor receptors in respiratory syncytial virus-infected lungs. 1211 13

Respiratory syncytial virus (RSV) infection is associated with exaggerated neurogenic inflammation in the airways. This study sought to determine whether irritation of the mucosal sensory fibers affects the recruitment of lymphocytes and monocytes to RSV-infected airways. Pathogen-free rats were inoculated with RSV or with virus-free medium and were injected 5 days later with capsaicin to stimulate airway sensory nerves. Bronchoalveolar lavage was performed 1, 5, or 10 days after nerve stimulation, and samples were analyzed by differential cell count and flow cytometry. Without nerve stimulation, RSV caused a minimal increase in the number of lymphocytes and monocytes above pathogen-free control levels. After nerve stimulation, numerous lymphocytes, predominantly CD4+ T cells, and monocytes were recruited in the airways of infected rats, whereas no difference was found in pathogen-free controls. RSV induced overexpression of the neurokinin 1 (NK1) receptor for substance P on discrete lymphocyte subpopulations within the bronchial-associated lymphoid tissue (BALT), and treatment with a specific NK1 receptor antagonist abolished the recruitment of both lymphocytes and monocytes to infected airways. Our data suggest that airborne irritants stimulating mucosal sensory fibers during RSV infection exert important immunomodulatory effects by attracting to the infected airways selected lymphocyte subpopulations from the local BALT as well as monocytes.
Am J Physiol Lung Cell Mol Physiol 2003 Jul
PMID:Immunomodulatory effects of sensory nerves during respiratory syncytial virus infection in rats. 1263 40


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