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Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251

BACKGROUND: The aim of this study was to evaluate gene therapy for AIDS based on the transduction of circulating lymphocytes with a retroviral vector giving low levels of constitutive macaque interferon β production in macaques chronically infected with a pathogenic isolate of SIVmac251. RESULTS: Tw...

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Autores principales: Gay, Wilfried, Lauret, Evelyne, Boson, Bertrand, Larghero, Jérome, Matheux, Franck, Peyramaure, Sophie, Rousseau, Véronique, Dormont, Dominique, De Maeyer, Edward, Le Grand, Roger
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC523856/
https://www.ncbi.nlm.nih.gov/pubmed/15447786
http://dx.doi.org/10.1186/1742-4690-1-29
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author Gay, Wilfried
Lauret, Evelyne
Boson, Bertrand
Larghero, Jérome
Matheux, Franck
Peyramaure, Sophie
Rousseau, Véronique
Dormont, Dominique
De Maeyer, Edward
Le Grand, Roger
author_facet Gay, Wilfried
Lauret, Evelyne
Boson, Bertrand
Larghero, Jérome
Matheux, Franck
Peyramaure, Sophie
Rousseau, Véronique
Dormont, Dominique
De Maeyer, Edward
Le Grand, Roger
author_sort Gay, Wilfried
collection PubMed
description BACKGROUND: The aim of this study was to evaluate gene therapy for AIDS based on the transduction of circulating lymphocytes with a retroviral vector giving low levels of constitutive macaque interferon β production in macaques chronically infected with a pathogenic isolate of SIVmac251. RESULTS: Two groups of three animals infected for more than one year with a pathogenic primary isolate of SIVmac251 were included in this study. The macaques received three infusions of their own lymphocytes transduced ex vivo with the construct encoding macaque IFN-β (MaIFN-β or with a vector carrying a version of the MaIFN-β gene with a deletion preventing translation of the mRNA. Cellular or plasma viremia increased transiently following injection in most cases, regardless of the retroviral construct used. Transduced cells were detected only transiently after each infusion, among the peripheral blood mononuclear cells of all the animals, with copy numbers of 10 to 1000 per 10(6 )peripheral mononuclear cells. CONCLUSION: Long-term follow-up indicated that the transitory presence of such a small number of cells producing such small amounts of MaIFN-β did not prevent animals from the progressive decrease in CD4(+ )cell count typical of infection with simian immunodeficiency virus. These results reveal potential pitfalls for future developments of gene therapy strategies of HIV infection.
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spelling pubmed-5238562004-10-22 Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251 Gay, Wilfried Lauret, Evelyne Boson, Bertrand Larghero, Jérome Matheux, Franck Peyramaure, Sophie Rousseau, Véronique Dormont, Dominique De Maeyer, Edward Le Grand, Roger Retrovirology Research BACKGROUND: The aim of this study was to evaluate gene therapy for AIDS based on the transduction of circulating lymphocytes with a retroviral vector giving low levels of constitutive macaque interferon β production in macaques chronically infected with a pathogenic isolate of SIVmac251. RESULTS: Two groups of three animals infected for more than one year with a pathogenic primary isolate of SIVmac251 were included in this study. The macaques received three infusions of their own lymphocytes transduced ex vivo with the construct encoding macaque IFN-β (MaIFN-β or with a vector carrying a version of the MaIFN-β gene with a deletion preventing translation of the mRNA. Cellular or plasma viremia increased transiently following injection in most cases, regardless of the retroviral construct used. Transduced cells were detected only transiently after each infusion, among the peripheral blood mononuclear cells of all the animals, with copy numbers of 10 to 1000 per 10(6 )peripheral mononuclear cells. CONCLUSION: Long-term follow-up indicated that the transitory presence of such a small number of cells producing such small amounts of MaIFN-β did not prevent animals from the progressive decrease in CD4(+ )cell count typical of infection with simian immunodeficiency virus. These results reveal potential pitfalls for future developments of gene therapy strategies of HIV infection. BioMed Central 2004-09-25 /pmc/articles/PMC523856/ /pubmed/15447786 http://dx.doi.org/10.1186/1742-4690-1-29 Text en Copyright © 2004 Gay et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open-access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Gay, Wilfried
Lauret, Evelyne
Boson, Bertrand
Larghero, Jérome
Matheux, Franck
Peyramaure, Sophie
Rousseau, Véronique
Dormont, Dominique
De Maeyer, Edward
Le Grand, Roger
Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251
title Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251
title_full Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251
title_fullStr Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251
title_full_unstemmed Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251
title_short Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251
title_sort low autocrine interferon beta production as a gene therapy approach for aids: infusion of interferon beta-engineered lymphocytes in macaques chronically infected with sivmac251
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC523856/
https://www.ncbi.nlm.nih.gov/pubmed/15447786
http://dx.doi.org/10.1186/1742-4690-1-29
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