Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry

Alteration of glucose metabolism specifically in immune cells has major health consequences. We monitored changes that took place in glycolytic enzymes, the pyruvate end product of glycolysis, tumor necrosis factor Ü (TNFÜ) and toll-like receptors (TLRs) both at the transcriptional and translational levels upon direct interaction between PR8-H1N1 and the human monocytes U937 in vitro system. Glucose concentration in this system was monitored following stimulation of the cells with pathogen or non-pathogen stimuli.U937 were first treated with H1N1 infectious viral particles or phorbol-12- myristate-13-acetate (PMA) or left untreated and later infected with H1N1 virus.Levels of phosphofructokinase 1 (PFK1) and pyruvate were biochemically quantified. Also, levels of TNFÜ, TLR3 and TLR7 were measured by ELISA. The transcriptional profiles of PFKs, inflammatory cytokines, TLR3 and TLR7 were relatively quantified by qRT-PCR.The results generally revealed significant changes in both the transcriptional and translational profiles of the studied biochemical and immunological parameters upon influenza infection in a time-dependent manner.Results showed also that regardless to whether the initial stimuli on U937 cells were of pathogen or non-pathogen origins, challenge infection by H1N1 causes a significant reduction of glucose levels 36 hours post infection. In conclusion, H1N1 infection has a direct effect on the glucose uptake of U937 cells in vitro and triggers transcriptional and translational changes in immortalized human monocytes which might serve as markers for infection subject for further validation for their specificities.

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