HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary Table Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gutierrez-Sanmartin, D. Articles by Regueiro, B. J. Search for Related Content PubMed PubMed Citation Articles by Gutierrez-Sanmartin, D. Articles by Regueiro, B. J. Agricola Articles by Gutierrez-Sanmartin, D. Articles by Regueiro, B. J.

Implication of p38 mitogen-activated protein kinase isoforms (, β, and ) in CD4⁺ T-cell infection with human immunodeficiency virus type I

¹ Clinical Microbiology, Hospital de Conxo, Complejo Hospitalario Universitario de Santiago (CHUS), 15706 Santiago de Compostela, Spain
² Rheumatology, Hospital Provincial, Complejo Hospitalario de Pontevedra (CHOP), Pontevedra, Spain
³ Facultad de Matematicas, Universidad de Santiago (Campus Sur), Santiago de Compostela, Spain

Correspondence
Benito J. Regueiro
mpbjrg{at}usc.es

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, p38β, 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 p38βdn 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 p38β, are implicated in both HIV-1 induced replication and apoptosis in infected and uninfected bystander cells.

A table showing the set of primers used in the construction of retroviral vectors is available with the online version of this paper.