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ORIGINAL RESEARCH ARTICLE

Different Sensitivity to Apoptosis in Cells of Monocytic or Lymphocytic Origin Chronically Infected with Human Immunodeficiency Virus Type-1

Marcello Pinti^*, Priscilla Biswas, Leonarda Troiano^*, Milena Nasi^*, Roberta Ferraresi^*, Cristina Mussini, Jacopo Vecchiet, Roberto Esposito, Roberto Paganelli and Andrea Cossarizza^*,1

^* Department of Biomedical Sciences, Section of General Pathology, University of Modena and Reggio Emilia School of Medicine, Modena, Italy;
Laboratory of Clinical Immunology, San Raffaele Scientific Institute, 20127 Milano, Italy;
Infectious Disease Clinics, University of Modena and Reggio Emilia School of Medicine, 41100 Modena, Italy; and
Department of Medicine and Sciences of Aging, University "G. d’Annunzio", 66100 Chieti, Italy

Apoptotic death of CD4+ T lymphocytes is a major cause of the immunodeficiency caused by human immunodeficiency virus (HIV), but it is still unclear how this process precisely occurs. To characterize a potentially useful cellular model, we have analyzed the tendency of chronically HIV-infected CD4+ human cell lines of different origin to undergo apoptosis. We studied ACH-2 and U1 lines, derived from the CD4+ T-cell A301 and the promonocytic U937 cell lines, respectively, and induced apoptosis via several stimuli that trigger different pathways. Their capacity to regulate plasma membrane CD95 expression and to produce soluble CD95 was also analyzed. Using staurosporine, TNF- plus cycloheximide, and -radiations, we observed that ACH-2 were more sensitive to programmed cell death than A301, while U1 were less sensitive than U937. Both infected cell types had a lower sensitivity to CD95-induced apoptosis; the analysis of changes in mitochondrial membrane potential corroborated these observations. Plasma membrane CD95 was similarly regulated in all cell types, which, however, presented a different capacity to produce soluble CD95 molecules.

Our in vitro results may offer a new perspective for developing further studies on the pathogenesis of HIV infection. A chronically infected cell line of lymphocytic origin is more susceptible to apoptosis than its parental cell type, while infected monocytic cells are less sensitive than their uninfected counterpart. Thus, it is possible to hypothesize that one of the reasons by which circulating monocytes survive and represent a viral reservoir is the capacity of HIV to decrease the sensitivity to apoptosis of this cell type. However, further studies on ex-vivo collected fresh cells, as well as on other cell lines, are urgently needed to confirm such hypothesis.

Key Words: HIV • AIDS • apoptosis • mitochondria • U1 • ACH-2

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