title: Redox regulation of T-cell turnover by the p13 protein of human T-cell leukemia virus type 1: distinct effects in primary versus transformed cells.
abstract: The present study investigated the function of p13, a mitochondrial protein of human T-cell leukemia virus type 1 (HTLV-1). Although necessary for viral propagation in vivo, the mechanism of function of p13 is incompletely understood. Drawing from studies in isolated mitochondria, we analyzed the effects of p13 on mitochondrial reactive oxygen species (ROS) in transformed and primary T cells. In transformed cells (Jurkat, HeLa), p13 did not affect ROS unless the cells were subjected to glucose deprivation, which led to a p13-dependent increase in ROS and cell death. Using RNA interference we confirmed that expression of p13 also influences glucose starvation-induced cell death in the context of HTLV-1-infected cells. ROS measurements showed an increasing gradient from resting to mitogen-activated primary T cells to transformed T cells (Jurkat). Expression of p13 in primary T cells resulted in their activation, an effect that was abrogated by ROS scavengers. These findings suggest that p13 may have a distinct impact on cell turnover depending on the inherent ROS levels; in the context of the HTLV-1 propagation strategy, p13 could increase the pool of "normal" infected cells while culling cells acquiring a transformed phenotype, thus favoring lifelong persistence of the virus in the host.
authors.affiliation: Department of Oncology and Surgical Sciences, Institute of Neuroscience at the Department of Biomedical Sciences, Università di Padova, Via Gattamelata 64, Padua, Italy.
authors.forename: Micol
authors.initials: M
authors.lastname: Silic-Benussi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cavallari
authors.forename: Nicola
authors.initials: N
authors.lastname: Vajente
authors.forename: Silvia
authors.initials: S
authors.lastname: Vidali
authors.forename: Luigi
authors.initials: L
authors.lastname: Chieco-Bianchi
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lisa
authors.forename: Daniela
authors.initials: D
authors.lastname: Saggioro
authors.forename: Donna M
authors.initials: DM
authors.lastname: D'Agostino
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ciminale
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D016086:Lentivirus / Q000235:genetics; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D014161:Transduction, Genetic
chemical_list: D017382:Reactive Oxygen Species; D012191:Retroviridae Proteins; C072813:rof protein, Human T-lymphotropic virus 1; D049452:Green Fluorescent Proteins