Redox Regulation by the HIV-1 Tat Transcriptional Factor

Abstract

Balance or homeostasis in biological systems is defined as the “maintenance of static, or constant, conditions in the internal environment.” Living systems are in a continual state of flux where many events occur simultaneously. Thus, constancy may be achieved only transiently because cells are exposed to changing environments with the end result that there is a redirection of cellular metabolism, altering the balance. Intracellular systems operate to reestablish the balance while the environmental stimulus is still present. Once the stimulus is removed, a different set of controls is invoked, again reestablishing the equilibrium. One example of such a system is the oxidant/antioxidant balance: Oxygen is necessary for life, but in excess, it produces toxicity via the generation of reactive oxygen intermediates. This balance may be altered genetically or via infectious diseases that include viral infections. In the context of a viral infection, morbidity and mortality may actually be increased by the ability of the virus to alter this balance and not by the cytopathic effect per se.

Inappropriate production of free radicals leads to an alteration of redox homeostasis, which compromises cellular ability to respond to additional insults. Cells affected in such ways are more susceptible and succumb to stresses more readily than cells whose balance is normal. What results is a “dose response” to stress. Some of the active oxygen species (AOS) that participate in alterations of this balance are the superoxide radical (O₂^•−), hydrogen peroxide (H₂O₂), the hydroxyl radical (•OH), and hypochlorous acid. O₂^•−, although not very reactive,...