u-0126 and Cytomegalovirus-Infections

u-0126 has been researched along with Cytomegalovirus-Infections* in 1 studies

Other Studies

1 other study(ies) available for u-0126 and Cytomegalovirus-Infections

ArticleYear
Human cytomegalovirus activation of ERK and myeloid cell leukemia-1 protein correlates with survival of latently infected cells.
    Proceedings of the National Academy of Sciences of the United States of America, 2012, Jan-10, Volume: 109, Issue:2

    The ability of human CMV (HCMV) to enter and establish a latent infection in myeloid cells is crucial for survival and transmission in the human population. Initial pathogen binding and entry triggers a number of antiviral responses, including the activation of proapoptotic cell death pathways, which must be countered during latency establishment. However, mechanisms responsible for a prosurvival state in myeloid cells upon latent HCMV infection remain completely undefined. We hypothesized that the cellular antiapoptotic machinery must be initially activated by HCMV to promote early survival events upon entry. Here we show that HCMV transiently protects nonpermissive myeloid cells from chemical and virus entry induced cell death by up-regulating a key myeloid cell survival gene, myeloid cell leukemia (MCL)-1 protein. The induction of MCL-1 expression was independent of viral gene expression but dependent on activation of the ERK-MAPK pathway by viral glycoprotein B. Inhibition of ERK-MAPK signaling, inhibition of HCMV fusion, antibody-mediated neutralization of glycoprotein B signaling or expression of a shRNA against MCL-1 all correlated with increased cell death in response to virus infection or chemical stimulation. Finally we show that activation of ERK-MAPK signaling impacts on long-term latency and reactivation in hematopoietic cells. Thus, HCMV primes myeloid cells for from the initial virus-cell encounter. Given the importance of ERK and MCL-1 for myeloid cell survival, the successful establishment of HCMV latency in myeloid progenitors begins at the point of virus entry.

    Topics: Apoptosis; Blotting, Western; Butadienes; Cytomegalovirus; Cytomegalovirus Infections; DNA Primers; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Gene Expression Regulation; Genetic Vectors; Humans; Imidazoles; Lentivirus; Myeloid Cell Leukemia Sequence 1 Protein; Myeloid Cells; Nitriles; Proto-Oncogene Proteins c-bcl-2; Pyridines; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Viral Envelope Proteins; Virus Internalization

2012