Retrovirus-Induced Oxidative Stress with Neuroimmunodegeneration Is Suppressed by Antioxidant Treatment with a Refined Monosodium α-Luminol (Galavit)

Abstract

ABSTRACT Oxidative stress is involved in many human neuroimmunodegenerative diseases, including human immunodeficiency virus disease/AIDS. The retrovirus ts 1, a mutant of Moloney murine leukemia virus, causes oxidative stress and progressive neuro- and immunopathology in mice infected soon after birth. These pathological changes include spongiform neurodegeneration, astrogliosis, thymic atrophy, and T-cell depletion. Astrocytes and thymocytes are directly infected and killed by ts 1. Neurons are not infected, but they also die, most likely as an indirect result of local glial infection. Cytopathic effects of ts 1 infection in cultured astrocytes are associated with accumulation of the viral envelope precursor protein gPr80 env in the endoplasmic reticulum (ER), which triggers ER stress and oxidative stress. We have reported (i) that activation of the Nrf2 transcription factor and upregulation of antioxidative defenses occurs in astrocytes infected with ts 1 in vitro and (ii) that some ts 1-infected astrocytes survive infection by mobilization of these pathways. Here, we show that treatment with a refined monosodium α-luminol (Galavit; GVT) suppresses oxidative stress and Nrf2 activation in cultured ts 1-infected astrocytes. GVT treatment also inhibits the development of spongiform encephalopathy and gliosis in the central nervous system (CNS) in ts 1-infected mice, preserves normal cytoarchitecture in the thymus, and delays paralysis, thymic atrophy, wasting, and death. GVT treatment of infected mice reduces ts 1-induced oxidative stress, cell death, and pathogenesis in both the CNS and thymus of treated animals. These studies suggest that oxidative stress mediates ts 1-induced neurodegeneration and T-cell loss.