Apoptotic DNA fragmentation, and its in vitro prevention by nicotinamide, in lymphocytes from HIV-1-seropositive patients and in HIV-1-infected MT-4 cells
✍ Scribed by A. Savarino; C. Martini; G. C. Orofino; C. Cantamessa; L. Castelli; P. G. Pich; A. Sinicco; A. Pugliese
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 177 KB
- Volume
- 15
- Category
- Article
- ISSN
- 0263-6484
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✦ Synopsis
Apoptosis seems to play an important role in the decline of CD4 T-cells in patients infected with HIV-1. Moreover, extensive interest in apoptosis comes from the observation that it correlates both with the progression and the severity of HIV-1 infection. A cross-sectional study was made to evaluate whether such correlation may also extend to the early phases of ex vivo apoptosis, after 20 h of culture. DNA fragmentation, a parameter associated with apoptosis, was evaluated with the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling (TUNEL) technique, which preferentially labels apoptosis in comparison to necrosis. The results obtained indicate that a negative correlation exists between the proportion of lymphocytes exhibiting DNA strand breaks and the absolute number of CD4 T-cells per ml. DNA fragmentation was signi®cantly higher in patients with AIDS or advanced HIV-1 infection as compared to asymptomatic patients or seronegative individuals. No signi®cant dierence was found in relation to antiretroviral therapy. Furthermore, the addition of nicotinamide to the cultures signi®cantly reduced DNA fragmentation of both in vitro HIV-1-infected MT-4 cells and lymphocytes from six HIV-1-seropositive individuals. The results of this study con®rm that DNA fragmentation, as an early marker of apoptosis, correlates with the severity of HIV-1 infection and suggest that nicotinamide may be involved in the modulation of HIV-1-related apoptosis.