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CCR5 as a Natural and Modulated Target for Inhibition of HIV
Calimmune, Inc., Los Angeles, California, CA 90024, USA
Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg-Hessen, 68167 Mannheim, Germany
Cellex GmbH, 01307 Dresden, Germany
* Author to whom correspondence should be addressed.
Received: 2 September 2013; in revised form: 2 December 2013 / Accepted: 11 December 2013 / Published: 30 December 2013
Abstract: 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.
Keywords: CCR5; C46; gene therapy; HIV; stem cell transplantation
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Cite This Article
MDPI and ACS Style
Burke, B.P.; Boyd, M.P.; Impey, H.; Breton, L.R.; Bartlett, J.S.; Symonds, G.P.; Hütter, G. CCR5 as a Natural and Modulated Target for Inhibition of HIV. Viruses 2014, 6, 54-68.
Burke BP, Boyd MP, Impey H, Breton LR, Bartlett JS, Symonds GP, Hütter G. CCR5 as a Natural and Modulated Target for Inhibition of HIV. Viruses. 2014; 6(1):54-68.
Burke, Bryan P.; Boyd, Maureen P.; Impey, Helen; Breton, Louis R.; Bartlett, Jeffrey S.; Symonds, Geoff P.; Hütter, Gero. 2014. "CCR5 as a Natural and Modulated Target for Inhibition of HIV." Viruses 6, no. 1: 54-68.