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Influence of p38 MAPK isoforms (alpha, beta, gamma and delta) in apoptosis induced by HIV-1 in CD4+ T lymphocyte-based cell lines

Abstract number: P1014

Gutierrez-Sanmartin D., Varela-Ledo E., Aguilera-Guirao A., Romero-Yuste S., Romero-Jung P., Gomez-Tato A., Regueiro B.J.

Background: The CD4+ T cell reduction characteristic of HIV-1 infection is thought to result, in addition from infected T cell death, mainly from uninfected bystander T cell apoptosis. Nevertheless, the immunologic and virologic mechanisms leading to T cell death during HIV-1 infection are not yet fully understood.

Objective: In the present study we analyse the individual implication of the p38 mitogen-activated protein kinase (MAPK) isoforms (alpha, beta, gamma and delta) in apoptosis induced by HIV-1, taking into account that HIV-1 replication is known to be blocked by p38 inhibitors.

Methods: We used the SupT1 cell line where death induced by HIV-1 mainly happened 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 p38 isoform and each wild-type p38 isoform as control. An EGFP 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 citometry.

Results: We found that survival in SupT1-based cell lines infected by HIV-1 was increased by dominant-negative p38alpha, p38gamma and p38delta isoforms, but not by the dominant-negative p38beta isoform. HIV-1 replication was delayed most by the dominant-negative p38delta isoform and to a lesser extent by dominant-negative p38alpha and p38gamma isoforms. Moreover, these three dominant-negative isoforms reduced apoptosis induced by HIV-1 in both infected and bystander cells.

Conclusions: These results suggest that, in SupT1 cell line, p38alpha, p38gamma and p38delta, but not p38beta, are implicated in HIV-1 replication and apoptosis induced by HIV-1 in infected and bystander cells.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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