1887

Abstract

The CD4 T-cell reduction characteristic of human immunodeficiency virus type 1 (HIV-1) infection is thought to result, in addition to infected T-cell death, mainly from uninfected bystander T-cell apoptosis. Nevertheless, the immunological and virological mechanisms leading to T-cell death during HIV-1 infection are not yet fully understood. In the present study, we analysed the individual implication of the p38 mitogen-activated protein kinase (MAPK) isoforms (p38, p38, p38 and p38) during apoptosis induced by HIV-1, taking into account that HIV-1 replication is known to be blocked by p38 inhibitors. For this purpose, we used the SupT1 cell line, where death induced by HIV-1 mainly occurs by uninfected bystander cell apoptosis. A variety of SupT1-based cell lines were constructed constitutively expressing, under the control of cytomegalovirus promoter (PCMV), each dominant-negative (dn) p38 isoform and each wild-type p38 isoform as a control. An enhanced green fluorescent protein marker gene, under the control of the HIV-1 promoter, was inserted in all of them. These cell lines were infected with HIV-1 and analysed by flow cytometry. We found that survival in SupT1-based cell lines infected by HIV-1 was increased by the p38dn, p38dn and p38dn isoforms, but not by the p38dn isoform. HIV-1 replication was delayed most by p38dn and to a lesser extent by p38dn and p38dn. Moreover, these three isoforms, p38dn, p38dn and p38dn, reduced apoptosis induced by HIV-1. These results suggest that, in SupT1-based cell lines, p38, p38 and p38, but not p38, are implicated in both HIV-1 induced replication and apoptosis in infected and uninfected bystander cells.

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2008-07-01
2024-03-28
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