%0 Journal Article
%T CCR5 as a Natural and Modulated Target for Inhibition of HIV
%A Bryan P. Burke
%A Maureen P. Boyd
%A Helen Impey
%A Louis R. Breton
%A Jeffrey S. Bartlett
%A Geoff P. Symonds
%A Gero H¨¹tter
%J Viruses
%D 2014
%I MDPI AG
%R 10.3390/v6010054
%X 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¡ªthis without detrimental effects to the host¡ªand 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.
%K CCR5
%K C46
%K gene therapy
%K HIV
%K stem cell transplantation
%U http://www.mdpi.com/1999-4915/6/1/54