title: The drug monosodium luminol (GVT) preserves thymic epithelial cell cytoarchitecture and allows thymocyte survival in mice infected with the T cell-tropic, cytopathic retrovirus ts1.
abstract: A mutant of MoMuLV, called ts1, causes an AIDS-like syndrome in susceptible strains of mice. In mice infected at birth, thymic atrophy, CD4+ T cell loss, body wasting, and death occur by approximately 30-40 days postinfection (dpi). We have shown previously that the death of ts1-infected cells is not caused by viral replication per se, but by oxidative stress and apoptosis following their accumulation the ts1 viral envelope precursor protein, gPr80(env). In infected mice treated with the antioxidant monosodium alpha-luminol (GVT), T cell loss and thymic atrophy are delayed for many weeks, and body wasting and death do not occur until long after infected, untreated control mice have died. We show here that GVT treatment of ts1-infected mice maintains the thymic epithelial cell (TEC) cytoarchitecture and cytokeratin gradients required for thymocyte differentiation. It also suppresses thymocyte reactive oxygen species (ROS) levels, upregulates and stabilizes levels of the antioxidant-regulating transcription factor Nrf2, and prevents accumulation of gPr80(env) in thymocytes. We conclude that GVT treatment can make ts1 a non-cytopathic virus for thymocytes, although it cannot prevent thymocyte infection. Since oxidative stress also contributes to the loss of T cells in HIV-AIDS, the antioxidant effects of GVT may make it a useful therapeutic adjunct to HAART treatment.
authors.affiliation: Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957, USA. vscofield@mdanderson.org
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Scofield
authors.forename: Mingshan
authors.initials: M
authors.lastname: Yan
authors.forename: Xianghong
authors.initials: X
authors.lastname: Kuang
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Derek
authors.initials: D
authors.lastname: Crunk
authors.forename: Paul K Y
authors.initials: PK
authors.lastname: Wong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology* / Q000821:virology; D002470:Cell Survival / Q000187:drug effects; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000276:immunology; D007108:Immune Tolerance; D007633:Keratins / Q000276:immunology; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D009154:Mutation; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D012192:Retroviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012191:Retroviridae Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology* / Q000821:virology
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D012191:Retroviridae Proteins; D007633:Keratins