Human immunodeficiency virus type 1 Tat protein modulates cell cycle and apoptosis in Epstein-Barr virus-immortalized B cells.
Patients infected with human immunodeficiency virus type 1 (HIV-1) develop a spectrum of B cell lymphoproliferative disorders ranging from polyclonal B cell activation to B cell lymphomas. While a direct role of Epstein-Barr virus (EBV) is well recognized for most of these lesions, recent findings have suggested that transactivator HIV-1 Tat protein might be involved in the pathogenesis of B cell lymphomas. Tat-expressing EBV-positive B cells were generated by transduction with a retroviral Tat-encoding vector. B(Tat+) cells expressed lower levels of anti-apoptotic protein Bcl-2 than parental and control B(Tat-) cells, generated by transduction with an empty retroviral vector, and were more prone to apoptosis upon serum withdrawal, as assessed by analysis of annexin V-stained cells and cleavage of poly-ADP-ribose-polymerase by caspase 3. Nevertheless, in serum starvation, B(Tat-) cells mainly exhibited the Rb hypo-phosphorylated form, underwent cell cycle arrest, and grew in single cell suspension, while B(Tat+) cells displayed the Rb hyper-phoshorylated form, progressed throughout the cell cycle, and retained the ability to grow in small clumps. Finding that B(Tat+) cells maintained proliferative capacity upon serum withdrawal suggests that cells expressing Tat have growth advantages among the EBV-driven cell proliferations and may originate B cell clones with more oncogenic potential.
Colombrino
Eva
E
Department of Oncology and Surgical Sciences, Section of Oncology, University of Padova, Padua, Italy.
Rossi
Elisabetta
E
Ballon
Gianna
G
Terrin
Liliana
L
Indraccolo
Stefano
S
Chieco-Bianchi
Luigi
L
De Rossi
Anita
A
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D016895:Culture Media, Serum-Free; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014764:Viral Proteins / Q000032:analysis / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
D017304:Annexin A5; D016895:Culture Media, Serum-Free; D015696:Gene Products, tat; D014764:Viral Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D020169:Caspases