Human immunodeficiency virus type 1 Tat protein modulates cell cycle and apoptosis in Epstein-Barr virus-immortalized B cells

Eva Colombrino, Elisabetta Rossi, Gianna Ballon, Liliana Terrin, Stefano Indraccolo, Luigi Chieco-Bianchi, Anita De Rossi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)539-548
Number of pages10
JournalExperimental Cell Research
Volume295
Issue number2
DOIs
Publication statusPublished - May 1 2004

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tat Gene Products
Human Herpesvirus 4
HIV-1
Cell Cycle
B-Lymphocytes
Apoptosis
B-Cell Lymphoma
Serum
Apoptosis Regulatory Proteins
Trans-Activators
Lymphoproliferative Disorders
Poly(ADP-ribose) Polymerases
Annexin A5
Starvation
Cell Cycle Checkpoints
Caspase 3
Suspensions
Clone Cells
Cell Proliferation

Keywords

  • Apoptosis
  • B cell lymphomas
  • Bcl-2
  • Cell cycle
  • EBV
  • HIV-1
  • Tat protein

ASJC Scopus subject areas

  • Cell Biology

Cite this

Human immunodeficiency virus type 1 Tat protein modulates cell cycle and apoptosis in Epstein-Barr virus-immortalized B cells. / Colombrino, Eva; Rossi, Elisabetta; Ballon, Gianna; Terrin, Liliana; Indraccolo, Stefano; Chieco-Bianchi, Luigi; De Rossi, Anita.

In: Experimental Cell Research, Vol. 295, No. 2, 01.05.2004, p. 539-548.

Research output: Contribution to journalArticle

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