Oxidative Stress during HIV Infection: Mechanisms and Consequences

Figure 1

Cellular sources of reactive oxygen species in HIV infection. Several HIV proteins enhance ROS production by different mechanisms. These viral proteins include amongst others the envelope protein Gp120, Tat, Nef, Vpr, and RT. The envelope protein Gp120 enhances ROS production via upregulation of cytochrome P450 2E1 (CYP2E1), proline oxidase (POX), and activation of NOX2 and NOX4. Tat protein induces spermine oxidase (SMO), an enzyme involved in catabolism of biogenic polyamines, and may impact mitochondrial function. Tat also activates NADPH (but not xanthine) oxidases and in particular Nox4, which in turn may induce other peroxide-generating enzymes involved in unfolded protein response (UPR) such as ER oxidoreductin 1α (Ero1α). Vpr protein interacts with adenine nucleotide translocator (ANT, a component of mitochondrial permeability transition pore (PTP)) that is implicated in Ca²⁺ influx into mitochondria. Nef protein can directly interact with the p22phox subunit of NADPH oxidases without affecting NOX expression. Finally, RT triggers ROS production by yet undiscovered mechanism(s).