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CCR5 as a Natural and Modulated Target for Inhibition of HIV

Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection—this without detrimental effects to the host—an...

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Autores principales: Burke, Bryan P., Boyd, Maureen P., Impey, Helen, Breton, Louis R., Bartlett, Jeffrey S., Symonds, Geoff P., Hütter, Gero
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917431/
https://www.ncbi.nlm.nih.gov/pubmed/24381033
http://dx.doi.org/10.3390/v6010054
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author Burke, Bryan P.
Boyd, Maureen P.
Impey, Helen
Breton, Louis R.
Bartlett, Jeffrey S.
Symonds, Geoff P.
Hütter, Gero
author_facet Burke, Bryan P.
Boyd, Maureen P.
Impey, Helen
Breton, Louis R.
Bartlett, Jeffrey S.
Symonds, Geoff P.
Hütter, Gero
author_sort Burke, Bryan P.
collection PubMed
description Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection—this without detrimental effects to the host—and transplantation of CCR5-delta32 stem cells in a patient with HIV (“Berlin patient”) achieved viral eradication. As a more feasible approach gene-modification strategies are being developed to engineer cellular resistance to HIV using autologous cells. We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) that down-regulates CCR5 and inhibits HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This construct, effective against multiple strains of both R5- and X4-tropic HIV-1, is being tested in Phase I/II trials by engineering HIV-resistant hematopoietic cells.
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spelling pubmed-39174312014-02-07 CCR5 as a Natural and Modulated Target for Inhibition of HIV Burke, Bryan P. Boyd, Maureen P. Impey, Helen Breton, Louis R. Bartlett, Jeffrey S. Symonds, Geoff P. Hütter, Gero Viruses Article Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection—this without detrimental effects to the host—and transplantation of CCR5-delta32 stem cells in a patient with HIV (“Berlin patient”) achieved viral eradication. As a more feasible approach gene-modification strategies are being developed to engineer cellular resistance to HIV using autologous cells. We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) that down-regulates CCR5 and inhibits HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This construct, effective against multiple strains of both R5- and X4-tropic HIV-1, is being tested in Phase I/II trials by engineering HIV-resistant hematopoietic cells. MDPI 2013-12-30 /pmc/articles/PMC3917431/ /pubmed/24381033 http://dx.doi.org/10.3390/v6010054 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Burke, Bryan P.
Boyd, Maureen P.
Impey, Helen
Breton, Louis R.
Bartlett, Jeffrey S.
Symonds, Geoff P.
Hütter, Gero
CCR5 as a Natural and Modulated Target for Inhibition of HIV
title CCR5 as a Natural and Modulated Target for Inhibition of HIV
title_full CCR5 as a Natural and Modulated Target for Inhibition of HIV
title_fullStr CCR5 as a Natural and Modulated Target for Inhibition of HIV
title_full_unstemmed CCR5 as a Natural and Modulated Target for Inhibition of HIV
title_short CCR5 as a Natural and Modulated Target for Inhibition of HIV
title_sort ccr5 as a natural and modulated target for inhibition of hiv
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917431/
https://www.ncbi.nlm.nih.gov/pubmed/24381033
http://dx.doi.org/10.3390/v6010054
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