HIV: no PUMA no death?

Salomoni, Paolo; Cossarizza, Andrea

doi:10.1038/sj.cdd.4401446

Cited by 3 publications

(2 citation statements)

References 15 publications

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“…Future studies will be designed to understand the role of PUMA in apoptosis induced by these viral proteins. Interestingly, PUMA has been shown to be a crucial target in the apoptosis induced by HIV,56 which further emphasizes its importance in the response to different viral proteins, with diverse functions. It will be interesting to find out whether p73 and PUMA are involved in the sensitivity of cancer cells to a variety of pro-apoptotic viruses, including oncolytic adenovirus.…”

Section: Discussionmentioning

confidence: 99%

Specific isoforms of p73 control the induction of cell death induced by the viral proteins, E1A or Apoptin

Klanrit

Flinterman

Odell³

et al. 2008

Cell Cycle

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A member of the p53 family, p73, has several isoforms and differentially regulates transcription of genes involved in the control of the cell cycle and apoptosis. We have previously shown efficient and p53-independent, tumor-specific cell death induced by the viral proteins E1A and Apoptin. Here, we demonstrate that the induction of apoptosis by these viral proteins involves activation of TAp73. Both E1A and Apoptin induced expression of endogenous TAp73 and the p53/p73 BH3-only pro-apoptotic target, PUMA, independently of the p53 function. Furthermore, exogenous expression of TAp73 isoforms, particularly TAp73β, sensitized cells to killing by both E1A and Apoptin, while expression of ΔNp73α blocked this activity. Besides, knockout of the p73 regulator, c-Abl, attenuated E1A-induced apoptosis. In accordance with the role of p73 in apoptosis induced by these viral proteins, overexpression of TAp73β strongly induced apoptosis in p53-deficient cancer cells in vitro and in HNSCC xenografts. Using a doxycycline-inducible system, we provide evidence for target selectivity and significant differences in protein stability for specific p73 isoforms, suggesting a diverse and pivotal role for p73 in response to various genotoxic agents. Collectively, our data show that in the absence of the p53 function, viral proteins E1A and Apoptin utilize the p73 pathway to induce efficient tumor cell death.

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Section: Discussionmentioning

confidence: 99%

Specific isoforms of p73 control the induction of cell death induced by the viral proteins, E1A or Apoptin

Klanrit

Flinterman

Odell³

et al. 2008

Cell Cycle

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“…130,180 Multinucleated giant cells that are derived from HIV infection-induced fusion of macrophages, microglial nodules, and perivascular mononuclear inflammation are hallmarks of HIV dementia pathology. [181][182][183] A clear association between the amount of circulating activated monocytes and the development of HIV dementia has been established, 184,185 which is likely caused by increased inflammatory mediators from these monocytes and/or infected monocytes that are increasingly trafficking into the brain. 186 Although brain macrophages and microglia from HIVinfected individuals may have neuroprotective properties, especially in the early phase of the infection, 187,188 their predominant roles in the pathogenesis of HIV dementia are neuroinflammatory and neurotoxic -through the increased expression of cytokines such as TNF-α, IL-1, interferon-α, and inducible nitric oxide synthase.…”

Section: Virotoxins From Hivmentioning

confidence: 99%

HIV treatment: mechanisms of neurotoxicity and implications for targeted therapy

Lu²

2012

NBHIV

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The central nervous system is known to act as a unique compartment where the human immunodeficiency virus (HIV) can replicate independently from the plasma and as a sanctuary in which the virus is largely protected from the host immune system and combination antiretroviral therapy. Although combination antiretroviral therapy has dramatically decreased the rate of HIV-caused mortality and associated diseases, neurological complications are increasingly common. However, our knowledge of the complicated pathogenesis and clinical symptoms of HIV-associated neurocognitive dysfunction is limited by a lack of complete understanding of the biology of HIV and its interaction with host cells in the central nervous system. This review focuses on the mechanisms of HIV entry and replication in the central nervous system, neurotoxicity caused by viral proteins and cytokine/chemokines derived from affected host cells, their implications for targeted therapy, and advances in the development of animal models for novel therapeutics in the context of combination antiretroviral therapy regimens.

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Retinoblastoma protein induction by HIV viremia or CCR5 in monocytes exposed to HIV-1 mediates protection from activation-induced apoptosis: ex vivo and in vitro study

Gekonge

Raymond

Yin

et al. 2012

Journal of Leukocyte Biology

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HIV: no PUMA no death?

Cited by 3 publications

References 15 publications

Specific isoforms of p73 control the induction of cell death induced by the viral proteins, E1A or Apoptin

Specific isoforms of p73 control the induction of cell death induced by the viral proteins, E1A or Apoptin

HIV treatment: mechanisms of neurotoxicity and implications for targeted therapy

Retinoblastoma protein induction by HIV viremia or CCR5 in monocytes exposed to HIV-1 mediates protection from activation-induced apoptosis: ex vivo and in vitro study

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