title: Intracellular accumulation of cell cycle regulatory proteins and nucleolin re-localization are associated with pre-lethal ultrastructural lesions in circulating T lymphocytes: the HIV-induced cell cycle dysregulation revisited.
abstract: The HIV-induced demise of CD4-T cells is thought to be a result of the execution of genetically programmed cell death that occurs in lymphoid tissue, where many resident T cells are chronically hyperactivated. Since HIV-induced alterations of cell cycle control has been often indicated as prominent mechanism of immune hyper activation and cause of apoptotic death, the signal pathway involved in cell cycle dysregulation of T lymphocytes from HIV infected patients was extensively studied. Here, we also demonstrate that circulating T lymphocytes leave lymphoid tissues with diffused regressive lesions (vacuolization, blebbing, nuclear evanescence and organelle swelling). Equally diffused are biochemical anomalies that accompany the overall disarrangement of cell structure, particularly the fragmentation and diffusion into the cytoplasm of C23/nucleolin, the intracellular accumulation of short lived regulatory proteins and the decrease in expression of membrane proteins. All this is something more than a cell cycle-related remodelling of cell morphology and biochemical mechanisms, and rather recalls a necrotic/oncotic cell damage. Since these changes are associated with adaptive mechanisms to hypoxia, we give evidence for alteration of cell cycle control developing in conditions of scarce energy supply.
authors.affiliation: Department of Hygiene, Public Health and Preventive Medicine, University of Messina, Messina, Italy. giusyvisalli@yahoo.it
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Visalli
authors.forename: Mirko
authors.initials: M
authors.lastname: Paiardini
authors.forename: Cristina
authors.initials: C
authors.lastname: Chirico
authors.forename: Barbara
authors.initials: B
authors.lastname: Cervasi
authors.forename: Monica
authors.initials: M
authors.lastname: Currò
authors.forename: Nadia
authors.initials: N
authors.lastname: Ferlazzo
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Bertuccio
authors.forename: Angelo
authors.initials: A
authors.lastname: Favaloro
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellicanò
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sturniolo
authors.forename: Pasquale
authors.initials: P
authors.lastname: Spataro
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ientile
authors.forename: Isa
authors.initials: I
authors.lastname: Picerno
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Piedimonte
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D056744:Cyclin B1 / Q000378:metabolism; D056741:Cyclin D / Q000378:metabolism; D006678:HIV; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure*; D054875:Ubiquitination; D000097796:Nucleolin
chemical_list: D018797:Cell Cycle Proteins; D056744:Cyclin B1; D056741:Cyclin D; D051793:Hypoxia-Inducible Factor 1; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin