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Effects of heme metabolism on HIV-1 latency reversal
Kompas, Maroš ; Mělková, Zora (advisor) ; Trejbalová, Kateřina (referee)
Progression of HIV infection in HIV-positive patients can now be successfully controlled by the combined antiretroviral therapy. However, due to persistence of the latent reservoir, HIV infection cannot be cured. The immune system nor current therapeutic approaches can target the pool of latently infected cells, thus strategies aiming at reactivation and subsequent elimination of the reservoir cells are recognized as possibly curative. This thesis has examined previously demonstrated latency-reversing capacity of heme arginate (HA), another redox modulator, and their synergism with Protein Kinase C inducer phorbol myristate acetate (PMA) to reactivate HIV-1 in the context of heme metabolism. HIV-1 reactivation was assessed by the intensity of green fluorescence in the model Jurkat cell line clone (A2), containing HIV-1 "mini-virus" (LTR-Tat-IRES-EFGP-LTR), as well as in the A2 cells stably transfected with plasmid vectors encoding cDNA for specific factors of heme metabolism and for control luciferase. While the administration of redox modulator alone did not stimulate expression from the HIV-1 LTR and HA reactivated the "mini-virus" only slightly, both compounds revealed a synergy with PMA in all cell lines studied. Basal and induced expression of EGFP was found variable in cells transfected with...
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Changes of the intracellular redox state during virus infections
Kompas, Maroš ; Mělková, Zora (advisor) ; Trejbalová, Kateřina (referee)
Viruses are infectious agens, which cause disruption of a host cellular redox homeostasis. This effect is mediated by cellular defense machinery or via viral gene products. In order to restore cellular redox enviroment, activation of cellular adaptive response takes place. That is mediated by transcription factor Nrf2, which leads to upregulation of gene expression of antioxidant enzymes. Under suboptimal redox condition, or by detecting foreign nucleic acid, redox sensitive transcription factor Nf-κB is also being activated, what leads to expresion of proteins mediating cellular imunne responses. It is important to remember that these proteins might show malignant effects to surrounding tissues during long term inflammations. With respect to that, viruses have evolved mechanisms, through which they are able to overcome or hijack these pathways, in order to propagate the infection. Key words: intracellular redox state, ROS, RNS, oxidative stress, antioxidant enzymes, regulation of gene expression, virus infections
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