CCR5 as a Natural and Modulated Target for Inhibition of HIV

Viruses

Bryan P. Burke¹  Maureen P. Boyd¹  Helen Impey¹  Louis R. Breton¹  Jeffrey S. Bartlett¹  Geoff P. Symonds¹ 

[1]Calimmune, Inc., Los Angeles, California, CA 90024, USA

[2] E-Mails:

关键词: CCR5;    C46;    gene therapy;    HIV;    stem cell transplantation;   

DOI  :  10.3390/v6010054

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.