CCR5 as a Natural and Modulated Target for Inhibition of HIV

• Main Authors: Bryan P. Burke, Maureen P. Boyd, Helen Impey, Louis R. Breton, Jeffrey S. Bartlett, Geoff P. Symonds, Gero Hütter
• Format: Article
• Language: English
• Published: MDPI AG 2013-12-01
• Series: Viruses
• Subjects: CCR5; C46; gene therapy; HIV; stem cell transplantation
• Online Access: http://www.mdpi.com/1999-4915/6/1/54

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.