Abstract | OBJECTIVE: 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. METHODS:
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). RESULTS: 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. CONCLUSION: 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.
|
Authors | G Piedimonte, D Corsi, M Paiardini, G Cannavò, R Ientile, I Picerno, M Montroni, G Silvestri, M Magnani |
Journal | AIDS (London, England)
(AIDS)
Vol. 13
Issue 10
Pg. 1159-64
(Jul 09 1999)
ISSN: 0269-9370 [Print] England |
PMID | 10416518
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Cyclin B
- RNA, Viral
- CDC2 Protein Kinase
|
Topics |
- Apoptosis
- Blotting, Western
- CD4 Lymphocyte Count
- CD4-Positive T-Lymphocytes
(immunology, metabolism)
- CD8-Positive T-Lymphocytes
(immunology, metabolism)
- CDC2 Protein Kinase
(metabolism)
- Cyclin B
(biosynthesis)
- Enzyme Activation
- HIV Infections
(immunology, virology)
- Humans
- Leukocytes, Mononuclear
(immunology, metabolism)
- Lymphocyte Activation
- RNA, Viral
(blood)
- T-Lymphocytes
(immunology, metabolism, physiology)
|