Authors: Dianzani U.; Bensi T.; Savarino A.; Sametti S.; Indelicato M.; Mesturini R.; Chiocchetti A.

Source: Current HIV Research, Volume 1, Number 4, October 2003 , pp. 405-417(13)

Publisher: Bentham Science Publishers

Abstract:

Direct cytopathic effects cannot explain the massive CD4+ T cell depletion in acquired immunodeficiency syndrome (AIDS) patients and several indirect mechanisms may be involved. A role has been proposed for apoptosis of uninfected lymphocytes, since lymphocytes from human immunodeficiency virus-1+ (HIV-1) individuals display increased levels of spontaneous apoptosis. This process may be ascribed in part to cell exhaustion by the chronic uncontrolled infection, but can also be directly induced by viral components, such as gp120, tat or nef. A key role is played by the death receptor Fas, but a role can also be played by other death receptors, such as the TNF and TRAIL receptors. By contrast, death of HIV-infected cells seems to be Fas-independent and driven by other viral components such as vpr and HIV proteases. A further role may be played by depletion of CD4+ T cell itself and hence the withdrawal of survival factors such as cytokines. Different ability of HIV strains to induce death of infected and uninfected cells might play a role in the clinical and biological differences displayed by HIV strains. A further variability may be ascribed to the intrinsic resistance of cells to apoptosis, which may depend on the individual genetic background or the use of drugs inhibiting apoptosis. The observation that when progression of HIV infection is slow due to “apoptosis-resistant” genetic backgrounds of the patients, or defective HIV-1 strains, or successful highly active antiretroviral therapy (HAART), generally also T cell apoptosis is low, suggests that HIV-infected subjects may benefit from therapies aimed to inhibit Fas function and / or spontaneous apoptosis.

Keywords: apoptosis; fas; tnf; alps

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1570162033485131

Affiliations: 1: Department of Medical Science, “A. Avogadro” University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy.

Publication date: 2003-10-01

More about this publication?

• Current HIV Research aims to cover all the latest and outstanding developments of HIV research. We invite comprehensive review articles and novel, pioneering work in the basic and clinical fields on all areas of HIV research, including virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Each issue of the journal contains a series of timely in-depth reviews and original research written by leaders in the field covering a range of current topics on HIV research. Periodically, the journal will invite guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.

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