HIV protease inhibitors modulate apoptosis signaling in vitro and in vivo

Stacey Rizza, Steffany A L Bennett, Shawn N. Whitehead, Andrew David Badley

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

HIV protease inhibitors are an integral part of effective anti-HIV therapy. The drugs block HIV protease, prevent proper packaging of HIV virions, and decrease the HIV viral burden in the peripheral blood of infected individuals. In addition to direct anti-viral effects, the HIV protease inhibitors also modulate apoptosis. A growing body of work demonstrates the anti-apoptotic effects of HIV protease inhibitors on CD4+ and CD8+ T cells during HIV infection. The mechanism of this apoptosis inhibition is supported by several proposed hypotheses for how they alter the fate of the cell, including preventing adenine nucleotide translocator pore function, which consequently prevents loss of mitochondrial transmembrane potential. More recently, the anti-apoptotic effects of the HIV protease inhibitors have been tested in non-HIV, non-immune cell, whereby protease inhibitors prevent apoptosis, and disease in animal models of sepsis, hepatitis, pancreatitis and stroke. Interestingly, when HIV protease inhibitors are used at supra-therapeutic concentrations, they exert pro-apoptotic effects. This has been demonstrated in a number of tumor models. Although it is unclear how HIV protease inhibitors can induce apoptosis at increased concentrations, future research will define the targets of the immunomodulation and reveal the full clinical potential of this intriguing class of drugs.

Original languageEnglish (US)
Pages (from-to)969-977
Number of pages9
JournalApoptosis
Volume12
Issue number5
DOIs
StatePublished - May 2007

Fingerprint

HIV Protease Inhibitors
Apoptosis
HIV
HIV Protease
Animal Disease Models
T-cells
Immunomodulation
Adenine Nucleotides
Product Packaging
Protease Inhibitors
Viral Load
Pharmaceutical Preparations
Pancreatitis
Virion
Membrane Potentials
Hepatitis
HIV Infections
In Vitro Techniques
Tumors
Sepsis

Keywords

  • Apoptosis
  • HIV protease inhibitors
  • Mitochondria
  • Neurons

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

HIV protease inhibitors modulate apoptosis signaling in vitro and in vivo. / Rizza, Stacey; Bennett, Steffany A L; Whitehead, Shawn N.; Badley, Andrew David.

In: Apoptosis, Vol. 12, No. 5, 05.2007, p. 969-977.

Research output: Contribution to journalArticle

Rizza, Stacey ; Bennett, Steffany A L ; Whitehead, Shawn N. ; Badley, Andrew David. / HIV protease inhibitors modulate apoptosis signaling in vitro and in vivo. In: Apoptosis. 2007 ; Vol. 12, No. 5. pp. 969-977.
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