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2.
J Hematother Stem Cell Res ; 9(4): 481-7, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10982246

ABSTRACT

The aging process of long-term self-renewing hematopoietic stem/progenitor cells is not yet completely understood and recent studies on antiapoptotic cell pathways have demonstrated a close linkage between telomerase activation and Bcl-2 deregulation in human cancer cells. The present work shows that human T cell leukemia virus type II (HTLV-II) Mo virions that have originated from the T cell line (C344), but not from the B cell line (BJAB), are critically involved in mediating survival and growth effects on hematopoietic precursors (represented by both the TF-1 CD34+ cell line and by peripheral blood-derived CD34+ cells) through the maintenance or enhancement of telomerase activity and the induction of bcl-2 expression. In addition, using an interleukin-3-dependent TF-1 cell line, it was demonstrated that IL-3 deprivation was sufficient to influence the levels of telomerase activity and Bcl-2 expression in CD34+ cells. Taken together, these findings suggest that, in appropriate conditions, extended hematopoietic progenitor cell survival and proliferation following HTLV-II exposure depends on a synergistic interaction between up-regulation of Bcl-2 and activation of telomerase activity.


Subject(s)
Antigens, CD34/analysis , Hematopoietic Stem Cells/enzymology , Hematopoietic Stem Cells/immunology , Human T-lymphotropic virus 2/physiology , Telomerase/metabolism , B-Lymphocytes/enzymology , B-Lymphocytes/virology , Gene Expression Regulation/drug effects , Hematopoietic Stem Cells/virology , Humans , Interleukin-3/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , T-Lymphocytes/enzymology , T-Lymphocytes/virology , Telomerase/drug effects , Tumor Cells, Cultured/virology , Virion/physiology
4.
Blood ; 95(9): 2760-9, 2000 May 01.
Article in English | MEDLINE | ID: mdl-10779418

ABSTRACT

The influence of human T-cell leukemia/lymphoma virus type II (HTLV-II) in individuals also infected with HIV-1 is poorly understood. To evaluate the reciprocal influence of HTLV-II and HIV-1 infection, primary peripheral blood mononuclear cell (PBMC) cultures from coinfected individuals were established in the presence of interleukin 2 (IL-2). In these cultures, the kinetics of HTLV-II replication always preceded those of HIV-1. Noteworthy, the kinetics of HIV-1 production were inversely correlated to the HTLV-II proviral load in vivo and its replication ex vivo. These observations suggested a potential interaction between the 2 retroviruses. In this regard, the levels of IL-2, IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured in the same coinfected PBMC cultures. Endogenous IL-2 was not produced, whereas IL-6 and TNF-alpha were secreted at levels compatible with their known ability to up-regulate HIV-1 expression. The HIV-suppressive CC-chemokines RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta were also determined in IL-2-stimulated PBMC cultures. Of interest, their kinetics and concentrations were inversely related to those of HIV-1 replication. Experiments were performed in which CD8(+) T cells or PBMCs from HTLV-II monoinfected individuals were cocultivated with CD4(+) T cells from HIV-1 monoinfected individuals separated by a semipermeable membrane in the presence or absence of antichemokine neutralizing antibodies. The results indicate that HTLV-II can interfere with the replicative potential of HIV-1 by up-regulating viral suppressive CC-chemokines and, in particular, MIP-1alpha. This study is the first report indicating that HTLV-II can influence HIV replication, at least in vitro, via up-regulation of HIV-suppressive chemokines. (Blood. 2000;95:2760-2769)


Subject(s)
HIV Infections/complications , HIV-1/physiology , HTLV-II Infections/complications , Lymphocytes/immunology , Lymphocytes/virology , Macrophage Inflammatory Proteins/blood , Virus Replication , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/virology , Adult , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , Cells, Cultured , Chemokine CCL3 , Chemokine CCL4 , Cytokines/blood , Female , HIV Infections/immunology , HIV Infections/virology , HIV-1/drug effects , HIV-1/isolation & purification , HTLV-II Infections/immunology , HTLV-II Infections/virology , Humans , Interleukin-2/pharmacology , Lymphocytes/drug effects , Macrophage Inflammatory Proteins/biosynthesis , Macrophage Inflammatory Proteins/pharmacology , Male , Proviruses/isolation & purification , Regression Analysis , Viral Load , Virus Replication/drug effects
5.
J Inorg Biochem ; 76(3-4): 277-84, 1999 Sep 30.
Article in English | MEDLINE | ID: mdl-10605841

ABSTRACT

Reaction of the title ligands (HPyTSC and HS(S)PPh2, respectively) with R2SnO (R = Me, Et, Bu) in ethanol (EtOH) afforded the complexes [SnMe2(PyTSC) (S2PPh2)].EtOH (1) and [SnR2(PyTSC) (S2PPh2)] (R = Et (2), Bu (3)). The structures of 1 and 2 were determined by single-crystal X-ray diffractometry. In both these complexes the tin atom is coordinated to an N,N,S-dentate thiosemicarbazonate ligand, an anisobidentate dithiophosphinato ligand and the two R groups. The coordination polyhedrons can be described as distorted pentagonal bipyramids. A comparative study of the IR spectra of 1, 2 and 3 indicates that the butyl complex has a similar structure. Multinuclear (1H, 13C, 31P and 119Sn) NMR data suggest that the structures of 1 and 2 probably remain in CDCl3 (or DMSO-d6) solution but compound 3 partially decomposes in these media. Preliminary results on the effects of the complexes on the proliferation and differentiation of FLC, CEM, U937, K562 and TOM-1 leukaemia cells, and on the clonogenic activity of K562 cells are also described.


Subject(s)
Organotin Compounds/chemistry , Organotin Compounds/pharmacology , Cell Differentiation/drug effects , Cell Division/drug effects , Crystallography, X-Ray , Humans , K562 Cells , Ligands , Magnetic Resonance Spectroscopy , Molecular Structure , Organotin Compounds/chemical synthesis , Spectrophotometry, Infrared
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