HIV infection is an emerging health issue in Libya, particularly among young adults. Human cytomegalovirus (HCMV) is a prevalent infectious agent that presents with subclinical and fatal diseases in immunosuppressed i...HIV infection is an emerging health issue in Libya, particularly among young adults. Human cytomegalovirus (HCMV) is a prevalent infectious agent that presents with subclinical and fatal diseases in immunosuppressed individuals including HIV-infected individuals. Although the impact of HCMV infection in HIV-positive patients is well documented in several regions, epidemiologic estimates concerning HCMV co-infection among HIV-infected individuals remain limited in Libya. Hence, this cross-sectional study was undertaken to derive data regarding the prevalence of active HCMV viremia among HIV-infected individuals undergoing antiretroviral therapy (ART) from Libya. A total of 90 consented HIV-infected subjects followed by the National Center for Disease Control (NCDC) of Benghazi/Libya were recruited in this study and investigated for HCMV-IgG, HCMV-IgM specific antibodies, detection of HCMV lower matrix phosphoprotein (pp65) antigen, and detection of HCMV-DNA using qPCR to assess the prevalence of HCMV viremia. We determined that 77 (85.56%) of subjects were seropositive for HCMV-IgG antibodies, whereas the seropositivity for HCMV-IgM was 3.33% (3/90 subjects). Our results also revealed that 4.44% (4/90) of participants had viral antigenemia based on the laboratory diagnosis of HCMV-pp65. Regarding the PCR, we were able to detect the DNA of HCMV only in 3/90 subjects (3.33%) suggesting an active viremic condition. The detection of HCMV DNA along with the HCMV-pp65 in HIV-positive individuals highlights the necessity of early diagnosis to manage the progression of the disease. Furthermore, we highly recommend the use of anti-HCMV therapy in viremic individuals in combination with ART to reduce the burden of HCMV complications.展开更多
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
The rapid increasing number of completed bacterial genomes provides a good opportunity to compare their proteomes. This study was undertaken to specifically compare and contrast their secretomes--the fraction of the p...The rapid increasing number of completed bacterial genomes provides a good opportunity to compare their proteomes. This study was undertaken to specifically compare and contrast their secretomes--the fraction of the proteome with predicted N-terminal signal sequences, both type Ⅰ and type Ⅱ. A total of 176 theoretical bacterial proteomes were examined using the ExProt program. Compared with the Gram-positives, the Gram-negative bacteria were found, on average, to contain a larger number of potential Sec-dependent sequences. In the Gram-negative bacteria but not in the others, there was a positive correlation between proteome size and secretome size, while there was no correlation between secretome size and pathogenicity. Within the Gram-negative bacteria, intracellular pathogens were found to have the smallest secretomes. However, the secretomes of certain bacteria did not fit into the observed pattern. Specifically, the secretome of Borrelia burgdoferi has an unusually large number of putative lipoproteins, and the signal peptides of mycoplasmas show closer sequence similarity to those of the Gramnegative bacteria. Our analysis also suggests that even for a theoretical minimal genome of 300 open reading frames, a fraction of this gene pool （up to a maximum of 20%） may code for proteins with Sec-dependent signal sequences.展开更多
文摘HIV infection is an emerging health issue in Libya, particularly among young adults. Human cytomegalovirus (HCMV) is a prevalent infectious agent that presents with subclinical and fatal diseases in immunosuppressed individuals including HIV-infected individuals. Although the impact of HCMV infection in HIV-positive patients is well documented in several regions, epidemiologic estimates concerning HCMV co-infection among HIV-infected individuals remain limited in Libya. Hence, this cross-sectional study was undertaken to derive data regarding the prevalence of active HCMV viremia among HIV-infected individuals undergoing antiretroviral therapy (ART) from Libya. A total of 90 consented HIV-infected subjects followed by the National Center for Disease Control (NCDC) of Benghazi/Libya were recruited in this study and investigated for HCMV-IgG, HCMV-IgM specific antibodies, detection of HCMV lower matrix phosphoprotein (pp65) antigen, and detection of HCMV-DNA using qPCR to assess the prevalence of HCMV viremia. We determined that 77 (85.56%) of subjects were seropositive for HCMV-IgG antibodies, whereas the seropositivity for HCMV-IgM was 3.33% (3/90 subjects). Our results also revealed that 4.44% (4/90) of participants had viral antigenemia based on the laboratory diagnosis of HCMV-pp65. Regarding the PCR, we were able to detect the DNA of HCMV only in 3/90 subjects (3.33%) suggesting an active viremic condition. The detection of HCMV DNA along with the HCMV-pp65 in HIV-positive individuals highlights the necessity of early diagnosis to manage the progression of the disease. Furthermore, we highly recommend the use of anti-HCMV therapy in viremic individuals in combination with ART to reduce the burden of HCMV complications.
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The rapid increasing number of completed bacterial genomes provides a good opportunity to compare their proteomes. This study was undertaken to specifically compare and contrast their secretomes--the fraction of the proteome with predicted N-terminal signal sequences, both type Ⅰ and type Ⅱ. A total of 176 theoretical bacterial proteomes were examined using the ExProt program. Compared with the Gram-positives, the Gram-negative bacteria were found, on average, to contain a larger number of potential Sec-dependent sequences. In the Gram-negative bacteria but not in the others, there was a positive correlation between proteome size and secretome size, while there was no correlation between secretome size and pathogenicity. Within the Gram-negative bacteria, intracellular pathogens were found to have the smallest secretomes. However, the secretomes of certain bacteria did not fit into the observed pattern. Specifically, the secretome of Borrelia burgdoferi has an unusually large number of putative lipoproteins, and the signal peptides of mycoplasmas show closer sequence similarity to those of the Gramnegative bacteria. Our analysis also suggests that even for a theoretical minimal genome of 300 open reading frames, a fraction of this gene pool （up to a maximum of 20%） may code for proteins with Sec-dependent signal sequences.
