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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Bibliographic Details
Published in:Viruses 2013-12, Vol.6 (1), p.54-68
Main Authors: Burke, Bryan P, Boyd, Maureen P, Impey, Helen, Breton, Louis R, Bartlett, Jeffrey S, Symonds, Geoff P, Hütter, Gero
Format: Article
Language:English
Subjects:
Biological Therapy - methods
C46
CCR5
CCR5 Receptor Antagonists
Chemokines
Clinical Trials as Topic
Gene therapy
Genetic Therapy - methods
Genotype & phenotype
Graft versus host disease
Hematopoietic Stem Cell Transplantation - methods
Hematopoietic Stem Cells - immunology
Hematopoietic Stem Cells - physiology
Hematopoietic Stem Cells - virology
HIV
HIV Infections - therapy
HIV Infections - virology
HIV-1 - immunology
HIV-1 - physiology
Human immunodeficiency virus
Human immunodeficiency virus 1
Humans
Immune system
Infections
Leukemia
Receptors, CCR5 - biosynthesis
Receptors, HIV - antagonists & inhibitors
Receptors, HIV - biosynthesis
Recombinant Fusion Proteins - biosynthesis
Recombinant Fusion Proteins - genetics
Stem cell transplantation
Viruses
West Nile virus
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Summary: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.
ISSN:1999-4915
1999-4915
DOI:10.3390/v6010054