2,007 research outputs found
Genome-wide screening of haploid stem cells for the discovery of essential genes for marburg virus infection
No full textIdentification of host proteins that serve as viral entry factors has enabled insights into virus particle internalization, tropism, and pathogenesis. In this context, haploid cells allow the study of gene knockouts, since recessive mutations will show a clear phenotype due to the absence of a 2nd gene copy. The study of highly pathogenic viruses (HiPVs) present significant challenges due to the requirement for BSL-4 containments. Indeed it has been proposed to use the Vesicular Stomatitis Virus (VSV) pseudotyped with glycoprotein of HiPVs to study the viral entry pathway.
To identify host factors required for Marburg virus infection, we used a mammalian haploid embryonic stem cells library for infection with a recombinant VSV expressing the Marburg virus glycoprotein (rVSV-M) instead of the native glycoprotein.
While wild-type cells massively died upon rVSV-M infection, a high number of cells survived within the mutagenized cells. Surviving cells were analyzed by next generation sequencing to identify the mutated genes. Statistical analysis provided a list of 7 genes, potentially involved in rVSV-M entry, which will be validated by infection of specific KO clones. Their role on the viral life cycle will be investigated
Genetic Polymorphism of Drug Metabolizing Enzymes. Implications for Toxicity of Drugs and Other Xenobiotics
No full textCarbon tetrachloride-induced lipid peroxidation dependent on an ethanol-inducible form of rabbit liver microsomal cytochrome P-450
No full textAbstractTreatment of rats with ethanol or rabbits with either imidazole or pyrazole, agents known to induce the ethanol-inducible form of liver microsomal cytochrome P-450 (P-450 LMeb), caused, compared to controls, 3–25-fold enhanced rates of CCl4-dependent lipid peroxidation or chloroform production in isolated liver microsomes. No significant differences were seen when the rate of CCl4-dependent lipid peroxidation was expressed relative to the amount of P-450 LMeb in the various types of microsomal preparations. In reconstituted membranous systems, this type of P-450 was a 100-fold more effective catalyst of CCl4 metabolism than either of the cytochromes P-450 LM2 or P-450 LM4. It is proposed that the induction of this isozyme provides the explanation on a molecular level for the synergism seen of ethanol on CCl4-dependent hepatotoxicity
Ethanol-Inducible Cytochrome P450 2E1. Regulation, Radical Formation and Toxicological Importance.
No full text
Concerning Cytochromes P450: Role in the Metabolism and Toxicity of Drugs and other Xenobiotics . Edited by Costas Ioannides.
No full text- …
