Implication of p38 mitogen-activated protein kinase isoforms (alpha, beta, gamma and delta) in CD4+ T-cell infection with human immunodeficiency virus type I.
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 (p38alpha, p38beta, p38gamma and p38delta) 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 p38alphadn, p38gammadn and p38deltadn isoforms, but not by the p38betadn isoform. HIV-1 replication was delayed most by p38deltadn and to a lesser extent by p38alphadn and p38gammadn. Moreover, these three isoforms, p38alphadn, p38gammadn and p38deltadn, reduced apoptosis induced by HIV-1. These results suggest that, in SupT1-based cell lines, p38alpha, p38gamma and p38delta, but not p38beta, are implicated in both HIV-1 induced replication and apoptosis in infected and uninfected bystander cells.
Clinical Microbiology, Hospital de Conxo, Complejo Hospitalario Universitario de Santiago (CHUS), 15706 Santiago de Compostela, Spain.
Dolores
D
Gutierrez-Sanmartin
Clinical Microbiology, Hospital de Conxo, Complejo Hospitalario Universitario de Santiago (CHUS), 15706 Santiago de Compostela, Spain.
Eduardo
E
Varela-Ledo
Clinical Microbiology, Hospital de Conxo, Complejo Hospitalario Universitario de Santiago (CHUS), 15706 Santiago de Compostela, Spain.
Antonio
A
Aguilera
Rheumatology, Hospital Provincial, Complejo Hospitalario de Pontevedra (CHOP), Pontevedra, Spain.
Susana
S
Romero-Yuste
Clinical Microbiology, Hospital de Conxo, Complejo Hospitalario Universitario de Santiago (CHUS), 15706 Santiago de Compostela, Spain.
Patricia
P
Romero-Jung
Facultad de Matematicas, Universidad de Santiago (Campus Sur), Santiago de Compostela, Spain.
Antonio
A
Gomez-Tato
Clinical Microbiology, Hospital de Conxo, Complejo Hospitalario Universitario de Santiago (CHUS), 15706 Santiago de Compostela, Spain.
Benito J
BJ
Regueiro
D017209:Apoptosis; D019677:Artificial Gene Fusion; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002460:Cell Line; D002470:Cell Survival; D005434:Flow Cytometry; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D007527:Isoenzymes; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D048051:p38 Mitogen-Activated Protein Kinases