Although much progress has been made in identifying the signaling pathways that mediate viral RNA-induced apoptosis and activation of interferon-stimulated genes, the role that bacterial RNA plays in regulating these ...Although much progress has been made in identifying the signaling pathways that mediate viral RNA-induced apoptosis and activation of interferon-stimulated genes, the role that bacterial RNA plays in regulating these responses has remained undetermined. Herein, we identified bacterial RNA as a novel inducer of the apoptotic cell death. Unlike the parental cells, STAT1 and STAT2 mutants display apoptotic defects which were reversed by restoring the expression of wild type proteins. While STAT1 mutants lacking tyrosine-701 or a functional SH2 domain were effective as the wild-type protein in restoring the apoptotic response, the mutant carrying a point mutation at serine-727 of STAT1 was resistant to bacterial RNA-induced apoptosis. We also determined that the lack of apoptosis in the STAT1 and STAT2 mutants was correlated with the constitutive and inducible activation of apoptosis regulating proteins. Furthermore, we show that bacterial RNA induces transcriptional activation of STAT1, STAT2, IRF1, and ISGF3, which was impaired in STAT1 or STAT2 mutants. These observations suggested that the participation of STATs in regulating the apoptotic response is independent of their downstream functions as cytokine-induced transcriptional activators. In addition to bacterial immunity, the results presented here may also have implications in cellular pathophysiology and RNA-based therapy.展开更多
Human cytomegalovirus (HCMV) is a ubiquitous DNA-containing herpesvirus causes severe and fatal diseases in immunocompromised patients and a prevalent cause of virus-associated birth defects. Blood transfusion donated...Human cytomegalovirus (HCMV) is a ubiquitous DNA-containing herpesvirus causes severe and fatal diseases in immunocompromised patients and a prevalent cause of virus-associated birth defects. Blood transfusion donated for neonates, pregnant women, and immunocom-promised patients should be adequately screened for evidences of CMV infection prior to use in clinical management. The effective national programmes for quality-assured screening of donated blood have not yet been fully established, hence this study was undertaken to assess whether any bloodborne-CMV infections pose a significant threat to the safety of the blood supplies. A total of 200 voluntary blood donor subjects admitted to the Blood Bank of Benghazi/Libya were screened for transfusion-transmissible CMV (TT-CMV) using a highly sensitive CMV total IgG and IgM antibody enzyme immunoassay as well as CMV pp65 anti-genemia assays. We determined that the overall seropositivity for IgG antibodies (80.50%) was higher than that of IgM antibodies (39.00%), but only 2 (1.00%) individuals out of these donors were seropositive for the CMV-antigenic protein pp65. The frequency of CMV infection based on gender was incomparable due to the small population number of blood-donated females. According to age, there was not influence of various age groups on prevalence of anti-CMV IgG antibodies, while a progressive increase in seropositivity of CMV-IgM antibodies with age was detected. The age groups were not significantly associated with CMV prevalence. In contrast, only 2 (1.00%) patients were shown to be positive for all three performed assays indicating a recurrent infection. Our findings prove a risk of primary transfusion-associated transmission of CMV and may provide a policy guidance on ensuring safe blood supplies accessible to all patients who require transfusion.展开更多
文摘Although much progress has been made in identifying the signaling pathways that mediate viral RNA-induced apoptosis and activation of interferon-stimulated genes, the role that bacterial RNA plays in regulating these responses has remained undetermined. Herein, we identified bacterial RNA as a novel inducer of the apoptotic cell death. Unlike the parental cells, STAT1 and STAT2 mutants display apoptotic defects which were reversed by restoring the expression of wild type proteins. While STAT1 mutants lacking tyrosine-701 or a functional SH2 domain were effective as the wild-type protein in restoring the apoptotic response, the mutant carrying a point mutation at serine-727 of STAT1 was resistant to bacterial RNA-induced apoptosis. We also determined that the lack of apoptosis in the STAT1 and STAT2 mutants was correlated with the constitutive and inducible activation of apoptosis regulating proteins. Furthermore, we show that bacterial RNA induces transcriptional activation of STAT1, STAT2, IRF1, and ISGF3, which was impaired in STAT1 or STAT2 mutants. These observations suggested that the participation of STATs in regulating the apoptotic response is independent of their downstream functions as cytokine-induced transcriptional activators. In addition to bacterial immunity, the results presented here may also have implications in cellular pathophysiology and RNA-based therapy.
文摘Human cytomegalovirus (HCMV) is a ubiquitous DNA-containing herpesvirus causes severe and fatal diseases in immunocompromised patients and a prevalent cause of virus-associated birth defects. Blood transfusion donated for neonates, pregnant women, and immunocom-promised patients should be adequately screened for evidences of CMV infection prior to use in clinical management. The effective national programmes for quality-assured screening of donated blood have not yet been fully established, hence this study was undertaken to assess whether any bloodborne-CMV infections pose a significant threat to the safety of the blood supplies. A total of 200 voluntary blood donor subjects admitted to the Blood Bank of Benghazi/Libya were screened for transfusion-transmissible CMV (TT-CMV) using a highly sensitive CMV total IgG and IgM antibody enzyme immunoassay as well as CMV pp65 anti-genemia assays. We determined that the overall seropositivity for IgG antibodies (80.50%) was higher than that of IgM antibodies (39.00%), but only 2 (1.00%) individuals out of these donors were seropositive for the CMV-antigenic protein pp65. The frequency of CMV infection based on gender was incomparable due to the small population number of blood-donated females. According to age, there was not influence of various age groups on prevalence of anti-CMV IgG antibodies, while a progressive increase in seropositivity of CMV-IgM antibodies with age was detected. The age groups were not significantly associated with CMV prevalence. In contrast, only 2 (1.00%) patients were shown to be positive for all three performed assays indicating a recurrent infection. Our findings prove a risk of primary transfusion-associated transmission of CMV and may provide a policy guidance on ensuring safe blood supplies accessible to all patients who require transfusion.
