HIV-1 Tat protein concomitantly down-regulates apical caspase-10 and up-regulates c-FLIP in lymphoid T cells

A potential molecular mechanism to escape TRAIL cytotoxicity

Davide Gibellini, Maria Carla Re, Cristina Ponti, Francesca Vitone, Isabella Bon, Greta Fabbri, Maria Grazia Di Iasio, Giorgio Zauli

Research output: Contribution to journalArticle

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Abstract

In this study, we showed the existence of a positive correlation between the amount of human immunodeficiency virus-type 1 (HIV-1) RNA in HIV-1 seropositive subjects and the plasma levels of TRAIL. Since it has been previously demonstrated that HIV-1 Tat protein up-regulates the expression of TRAIL in monocytic cells whereas tat-expressing lymphoid cells are more resistant to TRAIL cytotoxicity, we next investigated the effect of Tat on the expression/activity of both apical caspase-8 and -10, which play a key role in mediating the initial phases of apoptosis by TRAIL, and c-FLIP. Jurkat lymphoblastoid human T cell lines stably transfected with a plasmid expressing wild-type (HIV-1) tat gene showed normal levels of caspase-8 but significantly decreased levels of caspase-10 at both mRNA and protein levels with respect to Jurkat transfected with the control plasmid or with a mutated (cys22) non-functional tat cDNA. A significant decrease of caspase-10 expression/activity was also observed in transient transfection experiments with plasmid carrying tat cDNA. Moreover, c-FLIPL and C-FLIPS isoforms were up-regulated in tat-expressing cells at both mRNA and protein level in comparison with control cells. Taken together, these results provide a molecular basis to explain the resistance of tat-expressing Jurkat cells to apoptosis induced by TRAIL and, possibly, to other death-inducing ligands.

Original languageEnglish
Pages (from-to)547-556
Number of pages10
JournalJournal of Cellular Physiology
Volume203
Issue number3
DOIs
Publication statusPublished - Jun 2005

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Caspase 10
tat Gene Products
T-cells
Cytotoxicity
Viruses
HIV-1
Up-Regulation
Down-Regulation
Lymphocytes
T-Lymphocytes
Plasmids
Caspase 8
tat Genes
Complementary DNA
Apoptosis
Messenger RNA
Jurkat Cells
Transfection
Protein Isoforms
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

HIV-1 Tat protein concomitantly down-regulates apical caspase-10 and up-regulates c-FLIP in lymphoid T cells : A potential molecular mechanism to escape TRAIL cytotoxicity. / Gibellini, Davide; Re, Maria Carla; Ponti, Cristina; Vitone, Francesca; Bon, Isabella; Fabbri, Greta; Di Iasio, Maria Grazia; Zauli, Giorgio.

In: Journal of Cellular Physiology, Vol. 203, No. 3, 06.2005, p. 547-556.

Research output: Contribution to journalArticle

Gibellini, Davide ; Re, Maria Carla ; Ponti, Cristina ; Vitone, Francesca ; Bon, Isabella ; Fabbri, Greta ; Di Iasio, Maria Grazia ; Zauli, Giorgio. / HIV-1 Tat protein concomitantly down-regulates apical caspase-10 and up-regulates c-FLIP in lymphoid T cells : A potential molecular mechanism to escape TRAIL cytotoxicity. In: Journal of Cellular Physiology. 2005 ; Vol. 203, No. 3. pp. 547-556.
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