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


CONCLUSIONS
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.
University of Messina Centro di Patologia Comparata dei Retrovirus, Messina, Italy.
G
G
Piedimonte
D
D
Corsi
M
M
Paiardini
G
G
Cannavò
R
R
Ientile
I
I
Picerno
M
M
Montroni
G
G
Silvestri
M
M
Magnani
D017209:Apoptosis; D015153:Blotting, Western; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D019926:Cyclin B / Q000096:biosynthesis*; D004789:Enzyme Activation; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000502:physiology
D019926:Cyclin B; D012367:RNA, Viral; D016203:CDC2 Protein Kinase