| Background:Apoptosis is a common response of cells to infection with viruses. Apoptosis could be triggered in virus-infected cells directly by the virus, resulting in activation of families of specific cellular proteases, including the caspases, or through "indirect" pathways activated by the cellular immune responses to the virus. Apoptosis is generally considered to be an important factor in host defense that hastens the death of infected cells and thereby limits the replication and spread of the virus. It is thus not surprising that many viruses have evolved various mechanisms to inhibit or evade apoptosis. In some virus-infected diseases, apoptosis can play a significant role in pathogenesis and the host immune response is of direct relevance for vaccine development.Respiratory syncytial virus (RSV) major causes bronchiolitis and pneumonia, is the leading cause of lower respiratory tract infection in infants and young children and serious disease in premature infants and persons with congenital heart disease or compromised immune systems. RSV is also an important cause of community-acquired lower respiratory infection in the elderly and adults. Currently, an RSV vaccine is not yet available, although several live attenuated vaccine candidates areunder clinical trials. Literatures concerning apoptosis in RSV-infected cells have been searched by Pubmed index, but information concerning apoptosis in RSV-infected cells has been inconsistent and conflicting. Some studies identified that apoptosis could be induced in RSV-infected cells, through up-regulation of pro-apoptotic genes (interferon regulatory factor 1, interleukin-1 beta-converting enzyme ), through the Fas - FasL pathway, through strongly up-regulated the expression of tumor necrosis factor-related apoptosis-indue ing ligand (TRAIL) and its functional receptors death receptor 4(DR4) and DR5. Other studies implicated apoptosis is inhibited or delayed in RSV-infected cells RSV. In one case, RSV infection of cells induced the anti-apoptotic factor IEX-1L, Mcl-1. In a second case, treatment of RSV-infected cells with an inhibitor of phosphatidylinositol 3-kinase (PI-3K) resulted in more-rapid apoptosis, implying that under normal conditions signaling through the PI-3K pathway mediates an inhibition of RSV-induced apoptosis. Currently, the mechanisms and signaling pathways activated by RSV that result in airway epithelial cell apoptosis are not yet understood.Ribavirin, a synthetic nucleoside, is an antiviral agent that has shown in vitro activity against a broad spectrum of DNA and RNA viruses. Ribavin was approved for the treatment of RSV lower respiratory tract infection and licensed from America Food and Drug Administration (FDA). It has shown in vitro and in viva activity against RSV effect. However, the precise mechanism of its anti-RSV properties is unknown.AIMIn the present study, we investigated apoptosis during RSV infection in A549 cell and expression of pro- and anti-apoptotic genes. And we investigated apoptosis during simultaneous incubation of ribavirin and RSV in A549 cell and expression of pro- and anti-apoptotic genes.EXPERIMENTAL PROCEDURES Cells and virusA549 cells, a tumor cell line with properties of normal airway epithelial cells, were cultured in RPMI 1640 supplemented with 10% fetal bovine serum. To minimize effects of exogenous growth factors or cytokines in our system, we reduced the supplemented serum concentration to 0. 5% 24 h prior to and during all experiments with RSV infection. RSV strain Long grown in Hep-2 cells was used for infection. The stock virus titer was 10~8 PFU/ml. RSV was diluted to a multiplicity of infection (MOI) of 2 PFU per cell for all experimental treatments. Uninfected HEp-2 cell culture fluid was processed similarly for use in a mock infection. GroupsA549 cells were grown to 80% confluence in 100-mm tissue culture dishes, incubated 24 h in RPMI 1640 supplemented with 0. 5% fetal calf serum.RSV group: A549 cells were infected with RSV (M0I=2) for 2 h, the media were replaced with RPMI 1640 supplemented with 0...
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