Unscheduled cyclin B expression and p34 cdc2 activation in T lymphocytes from HIV-infected patients

• Published in: AIDS (London) Vol. 13; no. 10; pp. 1159 - 1164
• Main Authors: PIEDIMONTE, G, CORSI, D, PAIARDINI, M, CANNAVO, G, LENTILE, R, PICERNO, I, MONTRONI, M, SILVESTRI, G, MAGNANI, M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 09.07.1999
• Subjects: AIDS/HIV; Apoptosis; Biological and medical sciences; Blotting, Western; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CDC2 Protein Kinase - metabolism; Cdc32 kinase; Cyclin B - biosynthesis; Enzyme Activation; HIV Infections - immunology; HIV Infections - virology; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lymphocyte Activation; Medical sciences; p34 protein; RNA, Viral - blood; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - physiology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Human; Immunopathology; Enzyme; Pathogenesis; Transferases; Cyclin; AIDS; Activation; Gene expression; Immune deficiency; Infection; Regulation(control); Enzymatic activity; Kinase; Viral disease; Cell cycle; T-Lymphocyte; Intracellular
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-199907090-00003

To study the role of cell cycle regulation during HIV infection by investigating in vivo and in vitro cyclin B and p34 cdc kinase expression. Cyclin B expression was analysed by Western blot in CD4 and CD8 cells from 25 HIV-infected patients and 24 uninfected individuals. In eight patients, a sequential analysis was performed after initiation of antiretroviral therapy (ART), and correlations with CD4 cell count and HIV viremia were studied. Sequential changes in cyclin B expression and p34 cdc kinase expression and activity were also studied in lymphocytes activated in vitro with phytohaemagglutinin (PHA). Lymphocytes from untreated HIV-infected patients demonstrate persistent in vivo overexpression of cyclin B in both CD4 and CD8 cell subpopulations. When cells are stimulated to proliferate in vitro, biochemical events that characterize the entrance into the cell cycle [ornithine decarboxylase (ODC) activity, interleukin 2 production, interleukin 2 alpha-chain receptor (IL-2R, CD25) expression, total protein synthesis, total DNA synthesis] show similar timing and sequence in lymphocytes from HIV-infected and uninfected individuals. However, in peripheral blood lymphocytes (PBL) from HIV-infected patients, cyclin B and p34 cdc kinase show premature expression during the cell cycle. Both in vivo cyclin B overexpression and in vitro unscheduled cyclin B expression were almost completely reversed 2-4 weeks after initiation of effective ART. Increased and unscheduled expression of cyclin B and p34 cdc kinase is consistently observed in CD4 and CD8 cells from HIV-infected patients, both in vivo and after in vitro mitogenic stimulation. These alterations correlate with the level of viremia and may provide a link between the perturbation of lymphocyte proliferative homeostasis and the exaggerated propensity towards apoptosis.