24 research outputs found
Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions
Monkeypox virus (MPV) is a zoonotic Orthopoxvirus and a potential biothreat agent that causes human disease with varying morbidity and mortality. Members of the Orthopoxvirus genus have been shown to suppress antiviral cell defenses, exploit host cell machinery, and delay infection-induced cell death. However, a comprehensive study of all host genes and virus-targeted host networks during infection is lacking. To better understand viral strategies adopted in manipulating routine host biology on global scale, we investigated the effect of MPV infection on Macaca mulatta kidney epithelial cells (MK2) using GeneChip rhesus macaque genome microarrays. Functional analysis of genes differentially expressed at 3 and 7 hours post infection showed distinctive regulation of canonical pathways and networks. While the majority of modulated histone-encoding genes exhibited sharp copy number increases, many of its transcription regulators were substantially suppressed; suggesting involvement of unknown viral factors in host histone expression. In agreement with known viral dependence on actin in motility, egress, and infection of adjacent cells, our results showed extensive regulation of genes usually involved in controlling actin expression dynamics. Similarly, a substantial ratio of genes contributing to cell cycle checkpoints exhibited concerted regulation that favors cell cycle progression in G1, S, G2 phases, but arrest cells in G2 phase and inhibits entry into mitosis. Moreover, the data showed that large number of infection-regulated genes is involved in molecular mechanisms characteristic of cancer canonical pathways. Interestingly, ten ion channels and transporters showed progressive suppression during the course of infection. Although the outcome of this unusual channel expression on cell osmotic homeostasis remains unknown, instability of cell osmotic balance and membrane potential has been implicated in intracellular pathogens egress. Our results highlight the role of histones, actin, cell cycle regulators, and ion channels in MPV infection, and propose these host functions as attractive research focal points in identifying novel drug intervention sites
A novel HIV-1-encoded microRNA enhances its viral replication by targeting the TATA box region
Fluorescent protein-tagged Vpr dissociates from HIV-1 core after viral fusion and rapidly enters the cell nucleus
Improving Driver Assistance in Intelligent Transportation Systems: An Agent-Based Evidential Reasoning Approach
Providing accurate real-time traffic information is an inherent problem for intelligent transportation systems (ITS). In order to improve the knowledge base of advanced driver assistance systems (ADAS), ITS are strongly concerned with data fusion techniques of all kinds of sensors deployed over the traffic network. Driver assistance is devoid of a comprehensive evidential reasoning system on contextual information, more specifically when a combination involves inside and outside sensory information of the driving environment. In this paper, we propose a novel agent-based evidential reasoning system using contextual information. Based on a series of information handling techniques, specifically, the belief functions theory and heuristic inference operations to achieve a consensus about daily driving activity in automatically inferring. That is quite different from other existing proposals, as it deals jointly with the driving behavior and the driving environment conditions. A case study including various scenarios of experiments is introduced to estimate behavioral information based on synthetic data for prediction, prescription, and policy analysis. Our experiments show promising, thought-provoking results encouraging further research
Résilience et vulnérabilité chez des chefs d'établissement scolaire: une étude exploratoire
Human Parvovirus B19 Induces Cell Cycle Arrest at G(2) Phase with Accumulation of Mitotic Cyclins
Human parvovirus B19 infects specifically erythroid progenitor cells, which causes transient aplastic crises and hemolytic anemias. Here, we demonstrate that erythroblastoid UT7/Epo cells infected with B19 virus fall into growth arrest with 4N DNA, indicating G(2)/M arrest. These B19 virus-infected cells displayed accumulation of cyclin A, cyclin B1, and phosphorylated cdc2 and were accompanied by an up-regulation in the kinase activity of the cdc2-cyclin B1 complex, similar to that in cells treated with the mitotic inhibitor. However, degradation of nuclear lamina and phosphorylation of histone H3 and H1 were not seen in B19 virus-infected cells, indicating that the infected cells do not enter the M phase. Accumulation of cyclin B1 was persistently localized in the cytoplasm, but not in the nucleus, suggesting that B19 virus infection of erythroid cells raises suppression of nuclear import of cyclin B1, resulting in cell cycle arrest at the G(2) phase. The B19 virus-induced G(2)/M arrest may be the critical event in the damage of erythroid progenitor cells seen in patients with B19 virus infection
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Localization to the nucleolus is a common feature of coronavirus nucleoproteins and the protein may disrupt host cell division
The subcellular localization of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) (group I and group II coronaviruses, respectively) nucleoproteins (N proteins) were examined by confocal microscopy. The proteins were shown to localize either to the cytoplasm alone or to the cytoplasm and a structure in the nucleus. This feature was confirmed to be the nucleolus by using specific antibodies to nucleolin, a major component of the nucleolus, and by confocal microscopy to image sections through a cell expressing N protein. These findings are consistent with our previous report for infectious bronchitis virus (group III coronavirus) (J. A. Hiscox et al., J. Virol. 75:506-512, 2001), indicating that nucleolar localization of the N protein is a common feature of the coronavirus family and is possibly of functional significance. Nucleolar localization signals were identified in the domain III region of the N protein from all three coronavirus groups, and this suggested that transport of N protein to the nucleus might be an active process. In addition, our results suggest that the N protein might function to disrupt cell division. Thus, we observed that approximately 30% of cells transfected with the N protein appeared to be undergoing cell division. The most likely explanation for this is that the N protein induced a cell cycle delay or arrest, most likely in the G2/M phase. In a fraction of transfected cells expressing coronavirus N proteins, we observed multinucleate cells and dividing cells with nucleoli (which are only present during interphase). These findings are consistent with the possible inhibition of cytokinesis in these cells