Altering cell death pathways as an approach to cure HIV infection

Andrew David Badley, A. Sainski, F. Wightman, S. R. Lewin

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Recent cases of successful control of human immunodeficiency virus (HIV) by bone marrow transplant in combination with suppressive antiretroviral therapy (ART) and very early initiation of ART have provided proof of concept that HIV infection might now be cured. Current efforts focusing on gene therapy, boosting HIV-specific immunity, reducing inflammation and activation of latency have all been the subject of recent excellent reviews. We now propose an additional avenue of research towards a cure for HIV: targeting HIV apoptosis regulatory pathways. The central enigma of HIV disease is that HIV infection kills most of the CD4 T cells that it infects, but those cells that are spared subsequently become a latent reservoir for HIV against which current medications are ineffective. We propose that if strategies could be devised which would favor the death of all cells which HIV infects, or if all latently infected cells that release HIV would succumb to viral-induced cytotoxicity, then these approaches combined with effective ART to prevent spreading infection, would together result in a cure for HIV. This premise is supported by observations in other viral systems where the relationship between productive infection, apoptosis resistance, and the development of latency or persistence has been established. Therefore we propose that research focused at understanding the mechanisms by which HIV induces apoptosis of infected cells, and ways that some cells escape the pro-apoptotic effects of productive HIV infection are critical to devising novel and rational approaches to cure HIV infection.

Original languageEnglish (US)
Article numbere718
JournalCell Death and Disease
Volume4
Issue number7
DOIs
StatePublished - Jul 2013

Fingerprint

Virus Diseases
Cell Death
HIV
Apoptosis
Infection
Research
Genetic Therapy
Immunity
Therapeutics
Bone Marrow

Keywords

  • Apoptosis
  • Bcl2
  • Casp8p41
  • HIV cure
  • Latency

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience

Cite this

Altering cell death pathways as an approach to cure HIV infection. / Badley, Andrew David; Sainski, A.; Wightman, F.; Lewin, S. R.

In: Cell Death and Disease, Vol. 4, No. 7, e718, 07.2013.

Research output: Contribution to journalArticle

Badley, Andrew David ; Sainski, A. ; Wightman, F. ; Lewin, S. R. / Altering cell death pathways as an approach to cure HIV infection. In: Cell Death and Disease. 2013 ; Vol. 4, No. 7.
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